MDR3 rs2109505 and rs1202283 polymorphisms are associated with susceptibility to intrahepatic cholestasis of pregnancy: A meta-analysis.

BACKGROUND: Many studies have assessed the relationship between gene polymorphisms in multidrug resistance protein 3 (MDR3) and the risk of intrahepatic cholestasis of pregnancy (ICP); however, there are many conflicting narratives. OBJECTIVES: This meta-analysis was conducted to assess the association between MDR3 gene polymorphisms and ICP. MATERIAL AND METHODS: A multi-database search was conducted using Web of Science, Embase, PubMed, and Chinese Biomedical Literature (CBM) databases. Eleven eligible studies focusing on 4 single nucleotide polymorphisms (SNPs) in the MDR3 gene were selected for analysis. A fixedor random-effects model was utilized for allelic, dominant, recessive, and superdominant genes. RESULTS: The pooled results indicated a statistically significant association between MDR3 polymorphism rs2109505 and an increased risk of ICP in both the general population and the Caucasian population. No statistically significant associations were found between MDR3 polymorphism rs2109505 and ICP in Italian or Asian populations for the 4 genetic models. The MDR3 polymorphism rs1202283 was associated with susceptibility to ICP in both the general and Italian populations. CONCLUSION: The MDR3 rs2109505 and rs1202283 polymorphisms are associated with ICP susceptibility: however, they displayed no correlation with an increased risk of ICP.

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

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.