BACKGROUND AND STUDY AIMS: Biliary atresia (BA) is a devastating disease of infants, invariably leading to cirrhosis, end-stage liver disease, and death if untreated. The etiology of BA is unknown, although infectious, immune, and genetic causes have been suggested. This study was designed to investigate whether polymorphism of the ITGB2 (CD18) gene is associated with susceptibility to BA. METHODS: The ITGB2 gene promoter and 16 exons were genotyped following amplification and sequencing, with associations assessed using Fischer's exact test in 106 patients diagnosed with BA and 108 unrelated healthy controls. RESULTS: We found one single nucleotide polymorphism (SNP) in the ITGB2 promoter region (-680 C/T) and five SNPs in exons, including: -111 T/C in exon 1, 117 G/A in exon 3, 819 G/A in exon 7, 1101 C/A in exon 10, and 3'-UTR+145C/A in exon 16. There were no significant differences in genotype and allelic frequencies of any of the SNPs between controls and patients with BA in both the promoter and exons 1, 3, 7, and 10. 3'-UTR+145C/A showed a significant increase in the C allele frequency (OR = 2.19, 95% CI: 1.39-3.46, p = 0.0006) and a significant increase in the CC genotype (p = 0.001) in BA patients compared with healthy controls. Using a reporter gene assay, the construct that contained the risk allele (3'-UTR+145 C) showed significantly higher luciferase activity than the nonrisk A allele (p = 0.007). CONCLUSION: Our study provides the first evidence of a possible role of ITGB2 3'-UTR+145C/A polymorphism in the pathogenesis of BA.
BACKGROUND AND STUDY AIMS: Biliary atresia (BA) is a devastating disease of infants, invariably leading to cirrhosis, end-stage liver disease, and death if untreated. The etiology of BA is unknown, although infectious, immune, and genetic causes have been suggested. This study was designed to investigate whether polymorphism of the ITGB2 (CD18) gene is associated with susceptibility to BA. METHODS: The ITGB2 gene promoter and 16 exons were genotyped following amplification and sequencing, with associations assessed using Fischer's exact test in 106 patients diagnosed with BA and 108 unrelated healthy controls. RESULTS: We found one single nucleotide polymorphism (SNP) in the ITGB2 promoter region (-680 C/T) and five SNPs in exons, including: -111 T/C in exon 1, 117 G/A in exon 3, 819 G/A in exon 7, 1101 C/A in exon 10, and 3'-UTR+145C/A in exon 16. There were no significant differences in genotype and allelic frequencies of any of the SNPs between controls and patients with BA in both the promoter and exons 1, 3, 7, and 10. 3'-UTR+145C/A showed a significant increase in the C allele frequency (OR = 2.19, 95% CI: 1.39-3.46, p = 0.0006) and a significant increase in the CC genotype (p = 0.001) in BA patients compared with healthy controls. Using a reporter gene assay, the construct that contained the risk allele (3'-UTR+145 C) showed significantly higher luciferase activity than the nonrisk A allele (p = 0.007). CONCLUSION: Our study provides the first evidence of a possible role of ITGB2 3'-UTR+145C/A polymorphism in the pathogenesis of BA.
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
Authors: Ming Fu; Ledong Tan; Zefeng Lin; Vincent C H Lui; Paul K H Tam; Jonathan R Lamb; Yan Zhang; Huimin Xia; Ruizhong Zhang; Yan Chen Journal: Clin Sci (Lond) Date: 2021-04-16 Impact factor: 6.124
Authors: Ying Chen; Melissa A Gilbert; Christopher M Grochowski; Deborah McEldrew; Jessica Llewellyn; Orith Waisbourd-Zinman; Hakon Hakonarson; Joan E Bailey-Wilson; Pierre Russo; Rebecca G Wells; Kathleen M Loomes; Nancy B Spinner; Marcella Devoto Journal: PLoS Genet Date: 2018-08-13 Impact factor: 5.917