Polymorphism of ITGB2 gene 3'-UTR+145C/A is associated with biliary atresia.

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.