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Associations between UGT1A1 and SLCO1B1 polymorphisms and susceptibility to neonatal hyperbilirubinemia in Thai population.

ABSTRACT: Hyperbilirubinemia is the main mechanism that causes neonatal jaundice, and genetics is one of the risk factors of hyperbilirubinemia. Therefore, this study aims to explore the correlation between two genes, UGT1A1 and SLCO1B1, and hyperbilirubinemia in Thai neonates. One hundred thirty seven neonates were recruited from Division of Clinical Chemistry, Ramathibodi Hospital. UGT1A1*28 and *6 were determined by pyrosequencing whereas, SLCO1B1 388A > G and 521 T > C genetic variants were determined by TaqMan® real-time polymerase chain reaction. Neonates carrying with homozygous (AA) and heterozygous (GA) variants in UGT1A1*6 were significantly related to hyperbilirubinemia development compared with wild type (GG; P < 0.001). To the combined of UGT1A1, total bilirubin levels in homozygous variant were higher significantly than heterozygous variant and wild type (P = 0.002, P = 0.003, respectively). Moreover, SLCO1B1 combination was significant differences between the hyperbilirubinemia and the control group (P = 0.041). SLCO1B1 521 T > C variant provide protection for Thai neonatal hyperbilirubinemia (P = 0.041). There are no significant differences in UGT1A1*28 and SLCO1B1 388A > G for the different severity of hyperbilirubinemia. The combined UGT1A1*28 and *6 polymorphism is a strong risk factor for the development of severe hyperbilirubinemia in Thai neonates. Therefore, we suggest neonates with this gene should be closely observed to avoid higher severities of bilirubin.

SUBMITTER: Atasilp C

PROVIDER: S-EPMC9059389 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Associations between UGT1A1 and SLCO1B1 polymorphisms and susceptibility to neonatal hyperbilirubinemia in Thai population.

Atasilp Chalirmporn C Kanjanapipak Janjira J Vichayaprasertkul Jaratdao J Jinda Pimonpan P Tiyasirichokchai Rawiporn R Srisawasdi Pornpen P Prempunpong Chatchay C Chamnanphon Monpat M Puangpetch Apichaya A Vanwong Natchaya N Klongthalay Suwit S Jantararoungtong Thawinee T Sukasem Chonlaphat C

BMC pediatrics 20220502 1

Hyperbilirubinemia is the main mechanism that causes neonatal jaundice, and genetics is one of the risk factors of hyperbilirubinemia. Therefore, this study aims to explore the correlation between two genes, UGT1A1 and SLCO1B1, and hyperbilirubinemia in Thai neonates. One hundred thirty seven neonates were recruited from Division of Clinical Chemistry, Ramathibodi Hospital. UGT1A1*28 and *6 were determined by pyrosequencing whereas, SLCO1B1 388A > G and 521 T > C genetic variants were determined ...[more]

PMID: 35501760

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Project description:The potential for genetic variation to cause adult unconjugated hyperbilirubinemia is increasingly being recognized. However, the cumulative effects of genetic variants have not been fully illuminated. The current study aimed to investigate the effects of uridine diphospho-glucuronosyl transferase 1A1 (UGT1A1) and/or solute carrier organic anion transporter family member 1B (SLCO1B) polymorphic variants and their combined effects on mild unconjugated hyperbilirubinemia in Chinese adults. Fourteen genetic variants in the UGT1A1 or SLCO1B gene were genotyped through sequencing in 148 adults with unconjugated hyperbilirubinemia and 158 healthy controls. Variants c.-3275T > G, (TA)6>(TA)7, c.211G > A or c.1091C > T within the UGT1A1 gene as well as c.521T > C within the SLCO1B1 gene appear to be genetic risk factors for inherited unconjugated hyperbilirubinemia. After adjusting for covariates, the results of multivariate logistic regressions revealed that odds ratios (ORs) [(with 95% confidence interval (CI)] of these five variants were 2.35 (95% CI: 1.37-4.01, p = 0.002), 2.38 (95% CI: 1.35-4.20, p = 0.003), 2.99 (95% CI: 1.71-5.21, p < 0.001), 7.60 (95% CI: 1.99-28.96, p = 0.003), and 2.54 (95% CI: 1.27-5.11, p = 0.009), respectively. The OR for unconjugated hyperbilirubinemia is positively correlated with the cumulative number of these five variants in adults. And the greater the number of genetic variations, the higher the total bilirubin level. Adults carrying diplotype 3/4 (homozygous c.-3275T > G and heterozygous (TA)6>(TA)7) had higher bilirubin levels than those with diplotypes 1/3 (heterozygous c.-3275T > G and (TA)6>(TA)7)) or 1/4 (heterozygous c.-3275T > G) (P < 0.05). Similarly, bilirubin levels in individuals with diplotype 2/4 (heterozygous c.-3275T > G and c.211G > A) were higher than adults carrying diplotypes 1/2 (heterozygous c.211G > A) or 1/4 (P < 0.001). For subjects with heterozygous or homozygous variant c.211G> A, as the number of c.521T > C alleles variation increased, the incidence of unconjugated hyperbilirubinemia increased, but it was not statistically significant. Our results indicate that variants of UGT1A1 and/or SLCO1B1 have combined effects on Chinese adult mild unconjugated hyperbilirubinemia.

Project description:IntroductionGenetic polymorphisms of drug transporters influence drug transporter activity and alter pharmacokinetic profiles of the drugs. Organic anion transporting polypeptide 1B1 (OATP1B1) and breast cancer resistance protein (BCRP) are important transporters encoded by solute carrier organic anion transporter family member 1B1 (SLCO1B1) gene and ATP-binding cassette subfamily G member 2 (ABCG2) gene, respectively. Polymorphisms in these genes are associated with increased plasma statins concentrations, statin-induced myopathy and poor response to allopurinol treatment.PurposeWe explored allele and genotype frequencies of SLCO1B1 and ABCG2 genes including their predicted phenotypes in 53 Thai participants. Of these, 17 had chronic kidney disease and were on statins.Materials and methodsGenotyping analysis for SLCO1B1 c.521T>C (rs4149056), c.388A>G (rs2306283), g.-11187G>A (rs4149015), and ABCG2 c.421C>A (rs2231142) was done by using TaqMan® Real time PCR. All were tested for Hardy-Weinberg Equilibrium.ResultsMost of the participants (80%) had normal function haplotypes SLCO1B1 (*1A and *1B) while decreased (*5, *15, and *17) and unknown (*21) function haplotypes were less observed. Four phenotypes of SLCO1B1 were observed: 69.81% had normal function (*1A/*1A,*1A/*1B, and *1B/*1B), 13.21% had intermediate function (*1A/*17, *1B/*15 and *1B/*17), 9.43% had indeterminate function (*1A/*21 and *1B/*21) and 7.55% had low function (*5/*15, *15/*15, and *15/*17). ABCG2 c.421A allele frequency was 25%. The frequency of ABCG2 c.421CA and AA phenotypes were 37.7% and 5.7%, respectively. The allele and genotype frequencies observed are consistent with reports in Asians. However, there were differences in major allele distributions between Asians and Caucasians for SLCO1B1 c.388A>G; SLCO1B1 c.388G were highly found in Asians, but c.388A were more observed in Caucasians.ConclusionThis study showed that in the Thai population, there were 4 SNPs of SLCO1B1 and ABCG2 genes. This finding may be clinically applied to minimize inter-individual variability of drugs such as statins and allopurinol. Further study with a larger sample size is needed to assess the drug profiles and responses to treatment.

Dataset Information

Associations between UGT1A1 and SLCO1B1 polymorphisms and susceptibility to neonatal hyperbilirubinemia in Thai population.

Publications

Associations between UGT1A1 and SLCO1B1 polymorphisms and susceptibility to neonatal hyperbilirubinemia in Thai population.

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