Wison Laochareonsuk1, Piyawan Chiengkriwate1, Surasak Sangkhathat2. 1. Department of Surgery, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, 90110, Thailand. 2. Department of Surgery, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, 90110, Thailand. surasak.sa@psu.ac.th.
Abstract
BACKGROUND: A genome-wide association study in East Asians suggested a genetic association between biliary atresia (BA) and a cluster of variants within the Adducin 3 (ADD3) and ADD3 antisense RNA1 (ADD3-AS1) genes. Another study in Thai neonates reported an association between BA and rs17095355. To validate those findings, this study aimed to analyze the BA association with single nucleotide polymorphisms (SNPs) and the additive influence of ADD3 and ADD3-AS1 in Thai neonates. METHODS: DNAs from 56 BA cases and 166 controls were genotyped for rs2501577, rs11194981, rs12268910 (ADD3) and rs17095355 (ADD3-AS1), using TaqMan PCR. Genotype distributions were compared between the groups, and SNP-SNP interactions were analyzed by combination of allelotypes. RESULTS: The risk allele frequencies of rs2501577, rs11194981, and rs17095355 in the BA group were significantly higher than in the controls. Univariate analysis showed that recessive variants in the three SNPs were associated with BA risk at ORs of 1.81 (95% CI 1.32-2.50), 1.58 (95% CI 1.14-2.20) and 1.92 (95% CI 1.39-2.66), respectively. SNP-SNP interaction analysis showed that the SNP combination of the two genes rs17095355 and rs2501577 provided an additive increase in BA risk. CONCLUSION: ADD3 and ADD3-AS1 variants increased susceptibility to BA, suggesting that these genes may play an additive role in the pathogenesis of the disease. In addition, these interactions may give a clue to the overexpression of the ADD3 protein in the liver of BA patients.
BACKGROUND: A genome-wide association study in East Asians suggested a genetic association between biliary atresia (BA) and a cluster of variants within the Adducin 3 (ADD3) and ADD3 antisense RNA1 (ADD3-AS1) genes. Another study in Thai neonates reported an association between BA and rs17095355. To validate those findings, this study aimed to analyze the BA association with single nucleotide polymorphisms (SNPs) and the additive influence of ADD3 and ADD3-AS1 in Thai neonates. METHODS: DNAs from 56 BA cases and 166 controls were genotyped for rs2501577, rs11194981, rs12268910 (ADD3) and rs17095355 (ADD3-AS1), using TaqMan PCR. Genotype distributions were compared between the groups, and SNP-SNP interactions were analyzed by combination of allelotypes. RESULTS: The risk allele frequencies of rs2501577, rs11194981, and rs17095355 in the BA group were significantly higher than in the controls. Univariate analysis showed that recessive variants in the three SNPs were associated with BA risk at ORs of 1.81 (95% CI 1.32-2.50), 1.58 (95% CI 1.14-2.20) and 1.92 (95% CI 1.39-2.66), respectively. SNP-SNP interaction analysis showed that the SNP combination of the two genes rs17095355 and rs2501577 provided an additive increase in BA risk. CONCLUSION:ADD3 and ADD3-AS1 variants increased susceptibility to BA, suggesting that these genes may play an additive role in the pathogenesis of the disease. In addition, these interactions may give a clue to the overexpression of the ADD3 protein in the liver of BA patients.
Entities:
Keywords:
ADD3; Biliary atresia; Genetic association study; Single nucleotide polymorphism
Authors: Lin He; Patrick Ho Yu Chung; Vincent Chi Hang Lui; Clara Sze Man Tang; Paul Kwong Hang Tam Journal: Int J Mol Sci Date: 2022-04-27 Impact factor: 6.208