Association of gallstone and polymorphisms of UGT1A1*27 and UGT1A1*28 in patients with hepatitis B virus-related liver failure

Abstract

Genetic variation in UDP-glucuronosyltransferase 1A1 gene (UGT1A1) is a lithogenic risk factor for gallstone formation. This study aimed to assess genotype and allele frequencies of common UGT1A1 variants in patients with gallstone and hepatitis B virus (HBV)-related hepatic failure. This study enrolled 113 healthy individuals (CTRL), 54 patients with HBV infection (HBV), 134 patients with gallstone-free hepatic failure and HBV infection, and 34 patients with gallstone-related hepatic failure and HBV infection (GRHF). Peripheral venous blood samples were collected for genomic DNA isolation. Polymerase chain reaction amplification was carried out for UGT1A1, followed by direct sequencing. Analysis for genotype and allele frequencies of UGT1A1 variants (UGT1A1*6, UGT1A1*27, UGT1A1*28, and UGT1A1*60) was performed. The allele distributions of the four groups did not deviate from Hardy–Weinberg equilibrium. Allele (A) and genotype (CA) frequency distributions of UGT1A1*27 were significantly different between GRHF and CTRL, or between GRHF and HBV. GRHF and CTRL exhibited significant differences in allele (A) and genotype (CA) frequency distributions of UGT1A1*28. Linkage disequilibrium analysis suggested that haplotype G-G-[TA]7-T may be associated with gallstone in HBV-related hepatic failure. Our data reveal that UGT1A1*27 and UGT1A1*28 variants are significantly observed in patients with GRHF compared to healthy individuals.

Genetics of Gallstone Disease and Their Clinical Significance: A Narrative Review

“…A significant proportion of these mutations influence cholesterol synthesis or transport in various ways ( Table 1 ). 12 , 14 , 19 , 20 , 23 , 28 , 30 , 31 , 33 – 35 , 37 , 38 , 40 , 47 , 51 , 52 , 66 – 71 Notably, the most impactful genes are those belonging to the ABC transporter family, particularly the ABCG8 cholesterol transporter. Different genes play important roles in the pathogenesis of GS disease across various ethnicities.…”

“…A significant proportion of these mutations influence cholesterol synthesis or transport in various ways (Table 1). 12,14,19,20,23,28,30,31,[33][34][35]37,38,40,47,51,52,[66][67][68][69][70][71] Notably, While cholelithiasis is commonly observed, particularly among older adults, certain features should prompt consideration of a genetic basis for this condition (Fig. 2).…”

“…While this study raises interesting questions, it also has limitations in terms of generalizability and the presence of confounding factors related to liver injury in the context of HBV infection. 52 …”

“…51 In a more recent study, Zhuo et al assessed the association of GSs and the polymorphism of certain risk variants of UGT1A1 in Chinese patients who had experienced acute liver failure due to hepatitis B virus (HBV) infection. 52 Their investigation compared the distribution of frequently implicated risk variants of UGT1A1 (UGT1A16, UGT1A127, UGT1A128, and UGT1A160) among these patients, individuals with HBV without GSs, those with acute liver failure without HBV, and healthy controls. Through their analysis, they discovered that not only did these groups differ in their serum bilirubin levels, but also that the variants UGT1A127 and UGT1A128 were most strongly associated with acute liver failure in those with GSs.…”