- PMID
- Gene Name
- Molecular Event
- Function in UC
- 17166930
- UGT1A1
- polymorphism
- Pathogenesis
- Method
- [thymine-adenine(TA)]7 Polymorphism in UGT1A1 gen
- Summary
- it is concluded that UGT1A1 promoter region Polymorphism was not a risk factor for Neonatal jaundice.
- The frequency of UDP-glucuronosyltransferase 1A1 promoter region (TA)7 polymorphism in newborns and it's relation with jaundice. Journal of tropical pediatrics, 2007 Feb [Go to PubMed]
- Increased bilirubin formation and decreased bilirubin conjugation play an important role in the pathogenesis of the newborn jaundice. Although physiologic jaundice is seen in most of the newborns, there are many risk factors that affect the severity and duration of hyperbilirubinemia. The latest studies showed that the frequency and severity of neonatal jaundice have been increased when mutations of the gene coding UDP-glucuronosyltransferase(UGT)1A1 coexist with other risk factors. Healthy term newborns weighing over 2500 g. were included in this study. The patient group consisted of 107 newborns either with total bilirubin level over 15 mg dl(-1) within 7 days or 5 mg dl(-1) after 15 days of age. The control group consisted of 55 newborns with bilirubin levels in physiological ranges. We investigated the frequency of promoter region [thymine-adenine(TA)]7 polymorphism in UGT1A1 gene. Factors which might cause pathologic and prolonged jaundice with coexisting polymorphism were also investigated. UGT1A1 6/7 enotype was found to be 11% in patient group and 13% in the control group. The difference between patient and control groups was not statistically significant. (TA)7 allele frequency was 0.069 and it is concluded that UGT1A1 promoter region polymorphism was not a risk factor for neonatal jaundice.
- 11827650
- UGT1A1
- polymorphism
- Diagnosis
- Method
- (TA)7 instead of wild-type (TA)6
- Summary
- Prevalence of UGTA1A Polymorphism tended to be greater among jaundiced newborns (p 0.09
- [Interest in the study of genetic variants of the promoter region of the UGT1A1 gene in neonatal jaundice]. Anales españoles de pediatría, 2002 Feb [Go to PubMed]
- A relationship between polymorphism in the promoter region of the UGT1A1 gene (associated with Gilbert's syndrome) and the development of jaundice has recently been demonstrated. This polymorphism is due to (TA)7 instead of wild-type (TA)6.
To investigate the relationship between Gilbert's syndrome and neonatal jaundice by evaluating the distribution of (TA)7 in a population of newborns.
A total of 136 newborns were studied: 21 had neonatal jaundice, 69 were healthy and the remaining newborns had various diseases. DNA from each patient was used to amplify, by polymerase chain reaction, the promoter region of the UGT1A1 gene, which flanks the TATA box where the polymorphism is located.
In the group without jaundice, 53 % of the newborns were normal (6/6 genotype), 40 % were 6/7 and 7 % were 7/7. In the group with jaundice, 33 % of the newborns were normal, 53 % were heterozygous (6/7) and 14 % were homozygous (7/7). Comparison of the groups revealed that the prevalence of UGTA1A polymorphism tended to be greater among jaundiced newborns (p 0.09).
The results of this study suggest that there is a relationship between neonatal jaundice and Gilbert's syndrome among the Spanish population. These results, together with those of other authors, suggest that genetic screening for Gilbert's syndrome should be included in the investigation of neonatal jaundice in our population. Further studies with a greater number of subjects would determine the exact relationship between marked neonatal jaundice and IGTA1A polymorphism. Key words: - 20975617
- UGT1A1
- polymorphism
- Diagnosis; Pathogenesis
- Method
- promoter and exon1 of UGT1A1
- Summary
- This suggests that neonates who carry the nucleotide 211 GA or AA variation within coding region in UGT1A1 gene are more susceptible to develop early-onset neonatal breastfeeding jaundice.
- 211 G to a variation of UDP-glucuronosyl transferase 1A1 gene and neonatal breastfeeding jaundice. Pediatric research, 2011 Feb [Go to PubMed]
- Breastfeeding jaundice is a common problem in neonates who were exclusively breastfed, but its pathogenesis is still unclear. The uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1) gene polymorphism was shown to contribute to the development of neonatal hyperbilirubinemia. We hypothesize that the variation of UGT1A1 gene may contribute to neonatal breastfeeding jaundice. We prospectively enrolled 688 near-term and term infants who were exclusively breastfed (BF group) or were supplemented by infant formula partially (SF group) before onset of hyperbilirubinemia. Genotyping of the promoter and exon1 of UGT1A1 was performed in all neonates. Neonates in BF group had a significantly higher maximal body weight loss ratio, peak bilirubin level, and a greater incidence of hyperbilirubinemia than those in SF group. Neonates with nucleotide 211 GA or AA variation in UGT1A1 genotypes had higher peak serum bilirubin levels and higher incidence of hyperbilirubinemia than WTs (GG). This phenomenon was only seen inBF group but not in SF group when subset analysis was performed. This suggests that neonates who carry the nucleotide 211 GA or AA variation within coding region in UGT1A1 gene are more susceptible to develop early-onset neonatal breastfeeding jaundice.
- 11783956
- UGT1A1
- polymorphism
- Diagnosis; Pathogenesis
- Method
- NA
- Summary
- ADD A NOTE It indicates that enzyme levels are not normal in patients with G6PD A.
- Low glucose-6-phosphate dehydrogenase enzyme activity level at the time of hemolysis in a male neonate with the African type of deficiency. diseases, [Go to PubMed]
- Glucose-6-phosphate dehydrogenase (G6PD) levels are not usually drawn in the evaluation of black neonates with hyperbilirubinemia because of the oft-stated opinion that the levels may be normal at the time of hemolysis and thus will be misleading. In fact, this opinion is not applicable to newborns as many studies have shown that deficiency in the conjugating ability of the liver, not hemolysis, is the main cause of neonatal jaundice associated with G6PD deficiency. We present a case report of a neonate with brisk hemolysis and hyperbilirubinemia in whom the G6PD level was abnormally low at the time of the hemolytic episode. DNA analysis showed him to have the A-(202A,376G) variant and, as well, the UGT1A1 promoter repeat polymorphism associated with Gilbert's disease. This case, as well as a review of the literature, indicates that enzyme levels are not normal in patients with G6PD A- who are undergoing hemolysis.
- 20022574
- UGT1A1
- polymorphism
- Diagnosis; Pathogenesis
- Method
- NA
- Summary
- ADD A NOTE
- Exploring the genetic architecture of neonatal hyperbilirubinemia. neonatal medicine, 2010 Jun [Go to PubMed]
- The potential for genetic variation to modulate neonatal hyperbilirubinemia risk is increasingly being recognized. In particular, polymorphisms across three genes involved in bilirubin production and metabolism [glucose-6-phosphate dehydrogenase (G6PD), uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1), and solute carrier organic anion transporter polypeptide 1B1 (SLCO1B1)] may interact with each other and/or environmental contributors to produce significant hyperbilirubinemia. Variant gene co-expression including compound and synergistic heterozygosity enhances hyperbilirubinemia risk, contributing to the etiologic heterogeneity and complex nature of neonatal jaundice.
- 20207085
- UGT1A1
- polymorphism
- Diagnosis; Pathogenesis
- Method
- NA
- Summary
- ADD A NOTE
- The question of ethnic variability and the Darwinian significance of physiological neonatal jaundice in East Asian populations. Medical hypotheses, 2010 Aug [Go to PubMed]
- Recent work in Darwinian medicine has suggested that physiological neonatal jaundice (PNJ) might serve an adaptive function in scavenging reactive oxygen species that in later life are removed by the mature antioxidant enzyme system in the liver. This treatise examines this hypothesis in light of novel epidemiological and genetic findings which suggest that the incidence of PNJ is significantly increased in East Asian populations. Though found across all ethnic groups, it has been established that neonates of East Asian origin are at a significantly greater risk of developing PNJ, with more than one studying finding the incidence to be near double. For any Darwinian explanation of physiological neonatal jaundice to be considered in clinical circles, it is essential that the elevate incidence of PNJ in this population be explained both mechanistically and in terms of adaptation. Recent work has linked PNJ to a specific enzyme polymorphism, a variation of the UGT1A1 gene, in the glucoronidation pathway which is essential for bilirubin metabolism and is strongly correlated with ethnic origin. In this paper it is hypothesized that the elevated incidence of PNJ in East Asian populations is not random or due to a flaw in the system but rather due to an evolved mechanism. Two potential pressures which might have selected for an elevated neonatal bilirubin in East Asian populations versus other ethnic groups are a diminished ability to reduce harmful oxidant radicals due to variations the P450 liver metabolic pathway and the endemic nature of Hepatitis B in the Asia-Pacific region. This is the first work to attempt to explain PNJ through a Darwinian yet clinically relevant lens while suggesting a specific proximate mechanism that is correlated with a pre-existing evolutionary environment and an be associated with differential reproductive success.
- 11061796
- UGT1A1
- polymorphism
- Diagnosis
- Method
- NA
- Summary
- Sixteen the bilirubin UGT1A1 of infants with prolonged unconjugated hyperbilirubinemia,Seven were homozygous for 211G-->A (G71R), One was heterozygous for 1456T-->G (Y486D) and homozygous for 211G-->A. Six were heterozygous for 211G-->A. One was heterozygous for both 211G-->A and a TATA box mutation (A(TA)7TAA). One had a heterozygous mutation in an enhancer region (C-->A at -1353).
- Prolonged unconjugated hyperbilirubinemia associated with breast milk and mutations of the bilirubin uridine diphosphate- glucuronosyltransferase gene. Pediatrics, 2000 Nov [Go to PubMed]
- Breast milk jaundice is a common problem in nursing infants. It has been ascribed to various breast milk substances, but the component or combination of components that is responsible remains unknown. During our study of defects of the bilirubin uridine diphosphate-glucuronosyltransferase gene (UGT1A1) in patients with hereditary unconjugated hyperbilirubinemia (Crigler-Najjar syndrome and Gilbert's syndrome) and neonatal hyperbilirubinemia, we encountered a prolonged case associated with breastfeeding; after cessation of breastfeeding, the infant's bilirubin level became normal. Genetic analysis revealed a missense mutation identical to that found in patients with Gilbert's syndrome, which usually causes jaundice after puberty. We analyzed the bilirubin UGT1A1 of infants with prolonged unconjugated hyperbilirubinemia associated with breast milk to ascertain whether genetic factors are involved.
We analyzed 17 breastfed Japanese infants with apparent prolonged jaundice (total serum bilirubin concentrations above 171 micromol/L [10 mg/dL]) 3 weeks to 1 month after their birth. Except for jaundice, the infants were healthy and did not show evidence of hemolytic anemia, liver dysfunction, or hypothyroidism. After cessation of breastfeeding, the serum bilirubin concentration began to decrease in all cases. When breastfeeding was resumed, serum bilirubin concentration again became elevated in some infants, but the concentration fell to within normal by 4 months of age. We analyzed the polymerase chain reaction-amplified exon, promoter, and enhancer regions of UGT1A1 by direct sequencing.
Sixteen infants had at least one mutation of the UGT1A1. Seven were homozygous for 211G-->A (G71R), which is the most common mutation detected in the East Asian population, and the mutant enzyme had one third of the normal activity. G71R is the most common missense mutation we found in our analyses in Japanese patients with Gilbert's syndrome, and it corresponds to a UGT1A1 polymorphism in the Japanese population (the allele frequency is.16). One was heterozygous for 1456T-->G (Y486D) and homozygous for 211G-->A. Six were heterozygous for 211G-->A. One was heterozygous for both 211G-->A and a TATA box mutation (A(TA)7TAA). One had a heterozygous mutation in an enhancer region (C-->A at -1353). We did not detect a homozygous A(TA)7TAA mutation, which was the most common cause of Gilbert's syndrome in European population, in this study of Japanese infants with prolonged hyperbilirubinemia triggered by breast milk.
The results indicate that defects of UGT1A1 are an underlying cause of the prolonged unconjugated hyperbilirubinemia associated with breast milk. One or more components in the milk may trigger the jaundice in infants who have such mutations. The mutations we found were identical to those detected in patients with Gilbert's syndrome, a risk factor of neonatal nonphysiologic hyperbilirubinemia and a genetic factor in fasting hyperbilirubinemia. - 19325249
- UGT1A1
- polymorphism
- Diagnosis; Pathogenesis
- Method
- NA
- Summary
- There was a trend between the number of G71R mutations and the need for phototherapy.
- UGT1A1 haplotype mutation among Asians in Singapore. Neonatology, 2009 [Go to PubMed]
- The uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) enzyme is responsible for conjugation of the bilirubin in the liver as well as for drug metabolism. Some of the polymorphisms have been associated with an increased risk of neonatal hyperbilirubinemia which may explain the increased incidence of jaundice in an Asian population as well as exaggerated irinotecan-induced leukopenia.
The local Asian incidence of hypomorphic haplotypes, defined as gene mutations known to have a reduced function, has not been described. Clinical correlation between the mutations and the need for phototherapy for hyperbilirubinemia was carried out.
A cohort of 241 consecutive term infants delivered in the National University Hospital, Singapore, was recruited with parental consent. Cord blood was collected, and the promoter and coding regions of the UGT1A1 gene were sequenced.
Six known haplotypes and 2 novel haplotypes were identified: 1 wild type, 5 with reduced function, while the 2 novel ones were predicted to have decreased function. The frequency of these hypomorphic haplotypes was high. Among the 241 infants screened, 35% had 1 hypomorphic haplotype and 12% had 2 hypomorphic haplotypes. The frequency was also different among ethnic groups, with 48% Chinese, 64% Indian and 31% Malay infants having at least 1 hypomorphic haplotype (chi(2) test, p < 0.05). There was a trend seen between the number of G71R mutations and the need for phototherapy (chi2 test for trend, p < 0.05).
The local Asian incidence of hypomorphic haplotypes was high and there was a trend between the number of G71R mutations and the need for phototherapy. The G71R mutation may account for the increased incidence of neonatal jaundice seen in Asian populations. - 22407023
- UGT1A1
- polymorphism
- Diagnosis
- Method
- NA
- Summary
- We emphasize that investigating both the UGT1A gene and G6PD activity is the most reliable way to make a correct differential Diagnosis.
- Study of a family in the province of Matera presenting with glucose-6-phosphate dehydrogenase deficiency and Gilbert's syndrome. Molecular medicine reports, 2012 Jun [Go to PubMed]
- Glucose-6-phosphate dehydrogenase (G6PD) deficiency, a recessive X-linked trait, is the most common enzyme deficiency in the world. The most devastating clinical consequence of this deficit is severe neonatal jaundice, which results in sensorineural deficit, and severe haemolytic anemia. However, patients may be asymptomatic. The most common clinical sign is hyperbilirubinemia (h↑), that is also related to Gilbert's syndrome, a condition associated with the promoter polymorphism of the UDP-glucuronosyltransferase 1 (UGT1A1) gene. The aim of this study was to underline (as is usually done by DNA molecular analysis) to detect and to clarify the genetic deficiency that is the reason of the disorder in question. In this study, different techniques were applied to analyse a family of four individuals presenting with hyperbilirubinemia: bilirubinic dosage, electrophoresis and enzymatic activity dosage of G6PD; molecular analysis of the UGT1A promoter to detect a thymine-adenine (TA) insertion, that causes the[A(TA)7TAA] mutation. The results showed that in certain cases, the presence of hyperbilirubinemia is not only associated with G6PD deficiency, but may be caused by the co-presence of a mutation in the UGTA1 promoter related to Gilbert's syndrome. As being affected by these two conditions predisposes to adverse effects towards certain drug treatments, it is advisable to study the UGTA1 gene before prescribing drugs for specific antineoplastic or retroviral treatment. We emphasize that investigating both the UGT1A gene and G6PD activity is the most reliable way to make a correct differential diagnosis.
- 23981182
- UGT1A1
- polymorphism
- Diagnosis; Pathogenesis
- Method
- NA
- Summary
- These results further support the original Odell's idea of Neonatal jaundice as an early presentation of GS.
- Correlation of UGT1A1 TATA-box polymorphism and jaundice in breastfed newborns-early presentation of Gilbert's syndrome. neonatal medicine : the official journal of the E, 2014 May [Go to PubMed]
- The etiology of jaundice in otherwise healthy breastfed newborns that can present as early-onset exaggerated physiologic jaundice, or late breast milk jaundice (BMJ), is not yet entirely understood. This study tested the hypothesis that molecular marker for Gilbert's syndrome (GS), UGT1A1 TATA-box polymorphism, is associated with this disorders.
We have investigated the UGT1A1 polymorphism frequency and its relation to severity of hyperbilirubinemia and jaundice duration among 220 exclusively breastfed term newborns; 57 of them with non-physiologic hyperbilirubinemia (NH), and 163 with BMJ, and in 187 healthy controls.
Significant differences in TA7/7 genotype frequency were established. The highest frequency was observed among the newborns with BMJ (42.0%), intermediate in the NH group (24.6%), while the controls had the lowest TA7/7 frequency (12.8%). Linear increase in TA7/7 frequency was observed depending on the duration of jaundice, peaking at 42.4% in newborns with the longest jaundice duration. Positive correlation between the serum bilirubin levels and the TATA-box length was established in all groups.
This study provides evidence that UGT1A1 TATA-box polymorphism is an important risk factor for developing jaundice in term breastfed newborns, presented as either early non-physiologic hyperbilirubinemia or breast milk jaundice. These results further support the original Odell's idea of neonatal jaundice as an early presentation of GS. - 17506482
- UGT1A1
- polymorphism
- Diagnosis; Pathogenesis
- Method
- NA
- Summary
- This assay is rapid and robust for screening of SNP G211A to determine if this Polymorphism plays a role in causing severe Neonatal jaundice in the local context.
- Rapid detection of the UGT1A1 single nucleotide polymorphism G211A using real-time PCR with Taqman minor groove binder probes. Journal of clinical laboratory analysis, 2007 [Go to PubMed]
- The UGT1A1 Taqman MGB probe single nucleotide polymorphism (SNP) genotyping assay was developed to detect nucleotide 211 of the UDP-glucoronocyltransferase 1A1 (UGT1A1) gene. Defects in this enzyme interfere with process of conjugation of bilirubin and cause unconjugated hyperbilirubinemia. Variation at nucleotide 211 in the coding region of the UGT1A1 gene has been shown to be prevalent in Japanese and Chinese. Using an ABI sequence detection system (SDS) 7000, an allele-specific real-time PCR-based genotyping method was established to detect nucleotide G211A. Cord blood from 125 infants without hyperbilirubinemia (controls) were compared with cord blood from 74 infants (cases) with severe hyperbilirubinemia (total serum bilirubin > 300 micromol/L). Homozygous variation of the UGT1A1 gene at nucleotide 211(A/A) is significantly more common in cases (14.9%) than in controls (0.8%) (P<0.001). Direct sequencing from 20 randomly selected samples showed eight samples with homozygous wild type, seven with homozygous variant, and five samples were heterozygous. The result from this assay was in complete concordance with the DNA sequencing result and clearly discriminate wild-type (G/G), homozygous variant (A/A), and heterozygous (G/A). This assay is rapid and robust for screening of SNP G211A to determine if this polymorphism plays a role in causing severe neonatal jaundice in the local context.
- 11174102
- UGT1A1
- polymorphism
- Diagnosis
- Method
- NA
- Summary
- Gilbert syndrome (GS), characterized by mild, chronic and isolated unconjugated hyperbilirubinemia is due to a partial deficiency of bilirubin-UDP-glucuronosyltransferase (UGT1A1).
- [Refinement and role of the diagnosis of Gilbert disease with molecular biology]. Annales de biologie clinique, [Go to PubMed]
- Gilbert syndrome (GS), characterized by mild, chronic and isolated unconjugated hyperbilirubinemia is due to a partial deficiency of bilirubin-UDP-glucuronosyltransferase (UGT1A1). Recently, the genetic basis of GS has been identified in caucasian populations : it is related to the insertion of a dinucleotide (TA) in the promoter region of the UGT1A1 gene. In Asian populations, GS is due to missense mutations (either homozygous or heterozygous) in the coding sequence. The aim of this study was to develop a simple and rapid method to detect both genetic polymorphisms and mutations. This technique was performed (1) to explore unrelated unconjugated hyperbilirubinemia; (2) to evaluate the frequency of GS in a population of 97 healthy caucasian volunteers: 17% of them were homozygous for the TA7/TA7 polymorphism; (3) to determine the incidence of this syndrome in a population of 105 neonates with unconjugated hyperbilirubinemia. The incidence of GS (15%) was not significantly higher than it was in the control grup. A correlation between GS genotype and neonatal jaundice was not established; (4) to seek a relationship between GS and preeclampsia with or without Hellp syndrome. The incidence in the Hellp syndrome group (n = 19) was 26%, two fold higher than in preeclampsia group (n = 22) and control group (n = 50) with only 14% and 13% respectively, (5) to start a study regarding the toxicity of irinotecan treatment in a population of homozygous children for the UGT1A1 polymorphism.
- 16623861
- UGT1A1
- polymorphism
- Diagnosis; Pathogenesis
- Method
- NA
- Summary
- Our results do not suggest an association between thymine-adenine repeat Polymorphism of UGT1A1 and hyperbilirubinaemia of unexplained aetiology or prolonged jaundice in Turkish neonates.
- Neonatal jaundice and bilirubin UDP-glucuronosyl transferase 1A1 gene polymorphism in Turkish patients. toxicology, 2006 Apr [Go to PubMed]
- Bilirubin uridine diphosphate-glucuronosyltransferase (B-UGT) is the rate-limiting enzyme for the conjugation of bilirubin with glucuronic acid in its excretion process into the bile. Variations in B-UGT gene (UGT-1A1) have been related to disorders characterised by hyperbilirubinaemia. The aim of this study was to investigate whether the number of thymine-adenine repeats in the promoter region of UGT-1A1 was related to non-physiologic hyperbilirubinemia of unexplained aetiology in Turkish newborns. These patients (n=106) were genotyped for their thymine-adenine repeat number in the promoter region of UGT-1A1, and were divided into two groups according to their bilirubin level. Forty-nine newborns with bilirubin levels higher than 17 mg/dl within the first ten days of life comprised the hyperbilirubinaemia group and 25 newborns with bilirubin levels higher than 10 mg/dl after fifteen days of life formed the prolonged jaundice group. Thirty-two newborns were included as healthy controls. The observed frequences for the wild-type six repeat allele thymine-adenine (TA(6)) within each subject group were similar (P>0.05; 75.5%, 78.0% and 73.4%, respectively). Likewise, the distribution of TA(6/6), TA(6/7) and TA(7/7) genotypes among three groups were similar. These results imply that the TA(7) repeat allele of UGT1A1 (UGT1A1*28) is a common variant in the Turkish population. Our results do not suggest an association between thymine-adenine repeat polymorphism of UGT1A1 and hyperbilirubinaemia of unexplained aetiology or prolonged jaundice in Turkish neonates.
- 10190918
- UGT1A1
- polymorphism
- Diagnosis; Pathogenesis
- Method
- TATA box Polymorphism of the UGT1A1 gene
- Summary
- A genetic predisposition to develop prolonged Neonatal hyperbilirubinemia in breast-fed infants is associated with TATA box Polymorphism of the UGT1A1 gene and will be recognized as Gilbert's syndrome in adulthood and In addition to the known common UGT1A1 TATA alleles (TA6 and TA7), a novel TATA allele (TA5) in a neonate with very prolonged jaundice was identified.
- Gilbert's syndrome is a contributory factor in prolonged unconjugated hyperbilirubinemia of the newborn. The Journal of pediatrics, 1999 Apr [Go to PubMed]
- Prolonged neonatal jaundice, beyond day 14 of life, is very common and of concern to the clinician. The aim of this study was to investigate whether a genetic mutation in the bilirubin UGT1A1 gene, which has been associated with Gilbert's syndrome in adults, is a contributory factor in prolonged neonatal jaundice.
Blood was collected from 85 term newborns with unexplained hyperbilirubinemia, and DNA was prepared. The neonates were divided into 6 groups depending on whether they were breast-fed or bottle-fed and whether they had acute, prolonged, or very prolonged jaundice. UGT1A1 TATA promoter genotyping (DNA test for Gilbert's syndrome) was performed on all samples, and analysis of the entire UGT1A1 coding sequence was performed in a representative sample (11 of 26) of very prolonged cases.
In addition to the known common UGT1A1 TATA alleles (TA6 and TA7), a novel TATA allele (TA5) in a neonate with very prolonged jaundice was identified. Statistical analysis of the TATA genotype distributions within the group of breast-fed neonates revealed significant differences among the acute, prolonged, and very prolonged subgroups (.05 > P >.01): the incidence of familial hyperbilirubinemia genotypes (7/7 and 5/7) is 5 times greater in very prolonged cases (31%) relative to acute cases (6%). Neonates with prolonged jaundice from family pedigrees were observed to demonstrate the Gilbert's phenotype as children or young adults.
A genetic predisposition to develop prolonged neonatal hyperbilirubinemia in breast-fed infants is associated with TATA box polymorphism of the UGT1A1 gene and will be recognized as Gilbert's syndrome in adulthood. - 24783083
- UGT1A1
- polymorphism
- Diagnosis; inactive stage; Pathogenesis
- Method
- The promoter and coding regions of Uridine diphosp
- Summary
- We showed that in Gloucose-6-Phosphate Dehydrogenase (G6PD) deficient neonates, there was no significant association between Gilbert's syndrome (promoter Polymorphism) and hyperbilirubinemia.
- Relation between Neonatal Icter and Gilbert Syndrome in Gloucose-6-Phosphate Dehydrogenase Deficient Subjects. Journal of clinical and diagnostic research : JCDR, 2014 Mar [Go to PubMed]
- The pathogenesis of neonatal hyperbilirubinemia hasn't been completely defined in Gloucose-6-Phosphate Dehydrogenase (G6PD) deficient newborns. The aim of this study was to detect the relationship between Gilbert's syndrome and hyperbilirubinemia in Gloucose-6-Phosphate Dehydrogenase (G6PD) deficient neonates.
This case-control study was conducted in Amirkola pediatrics teaching hospital, Babol, Iran. A total number of one hundred four infants were included in the study (51 infants with neonatal jaundice and Gloucose-6-Phosphate Dehydrogenase (G6PD) deficiency admitted to phototherapy or transfusion were selected as the case group and 53 infants with Gloucose-6-Phosphate Dehydrogenase (G6PD) deficiency admitted for other reasons than jaundice were selected as the control group). Exclusion criteria were ABO or Rh incompatibility or other reasons that made Coombs test positive, sepsis, hepatosplenomegaly, metabolic diseases, medical treatment and phototherapy. The promoter and coding regions of Uridine diphosphate Glucuronosyl Transferase 1A1 (UGT1A1) of genomic DNA were amplified by polymerase chain reaction (PCR) isolated from leukocytes. We used chi-square test and t-test to compare cases and controls.
Distribution of Gilbert genome was not significantly different between the two groups; among cases, 33.3% were homozygote, 35.3% heterozygote, and 31.4% normal. Among controls, 22.6% were homozygote, 34% heterozygote, and 43.4% normal (p-value=xxx). Hyperbilirubinemia family history didn't differ significantly between these two groups.
We showed that in Gloucose-6-Phosphate Dehydrogenase (G6PD) deficient neonates, there was no significant association between Gilbert's syndrome (promoter polymorphism) and hyperbilirubinemia. - 20061399
- UGT1A1
- polymorphism
- Diagnosis; inactive stage; Pathogenesis
- Method
- promoter region of UGT1A1 gene
- Summary
- In this sample, the variants of UGT1A1 were not associated to severe hyperbilirubinemia;
- Polymorphic variants of UGT1A1 in neonatal jaundice in southern Brazil. Journal of tropical pediatrics, 2010 Oct [Go to PubMed]
- Alterations in the hepatic conjugation of bilirubin due to uridyl-diphosphate-glucuronosyltransferase 1A1 (UGT1A1) polymorphisms have been proposed as risk factors to neonatal jaundice. Herein, we estimated the frequency of genotypes of the promoter region of UGT1A1 gene in newborns and evaluated its association with severe hyperbilirubinemia. Prospective study of cases and controls including all newborns admitted for phototherapy at HCPA, Brazil, during 9 months; 490 babies were enrolled and PCR was performed. Polymorphic genotypes were detected in 16% of the patients and 7 of the 10 possible genotypes were identified with higher prevalence of polymorphisms in Afro-descendants. In this sample, the variants of UGT1A1 were not associated to severe hyperbilirubinemia; other genic factors should be sought in this high miscegenation area of Brazil.
- 12743455
- UGT1A1
- polymorphism
- Diagnosis; Pathogenesis
- Method
- NA
- Summary
- In conclusion, we showed that TA 7/7 and TA 6/7 genotypes are not rare in our population and that the presence of thes Polymorphisms alone does not play a significant role in the etiology of unexplained pathologic or prolonged Neonatal hyperbilirubinemia.
- Analyses of polymorphism for UGT1*1 exon 1 promoter in neonates with pathologic and prolonged jaundice. Biology of the neonate, 2003 [Go to PubMed]
- In this study, we investigated whether a TATA box polymorphism in the promoter of the UGT1*1 exon I, the most common detected DNA polymorphism in Gilbert's syndrome, is a contributory factor in unexplained pathologic or prolonged jaundice. 38 neonates who had unexplained pathologic jaundice, 37 neonates who had unexplained prolonged jaundice, and 35 healthy, nonjaundiced neonates were enrolled in the study. Genotypes were assigned as follows: 6/6 (homozygous for a normal allele bearing the sequence [TA](6)TAA), 7/7 (homozygous for an abnormal allele with the sequence [TA](7)TAA), and 6/7 (heterozygous with one of each allele). Of the 110 infants, 10 (9%) had 7/7, 51 (46%) had 6/7, and 49 (45%) had 6/6 genotype; the differences between the three groups were not statistically significant. Also no differences were observed among different genotypes and mean serum total bilirubin concentrations. In conclusion, we showed that TA 7/7 and TA 6/7 genotypes are not rare in our population and that the presence of thes polymorphisms alone does not play a significant role in the etiology of unexplained pathologic or prolonged neonatal hyperbilirubinemia.
17 pubmed articles have reported UGT1A1 polymorphism associated with Neonatal Jaundice.