The ABCB1 gene (formerly MDR1) encodes one member of the ATP-binding cassette super family of membrane transporters

that actively effluxes a wide range of compounds from cells. It is involved in multidrug resistance and antiapoptosis.43 Up-regulated expression of ABCB1 in human hepatocytes and bile ductules in viral hepatitis may offer protection against the accumulation of toxic bile constituents and render these cells resistant to oxidative stress.44 The 3435C>T (I1145I) variant (rs1045642) represents a main functional polymorphism, leading to changes in ABCB1 messenger RNA level, protein expression, protein folding, and substrate specificity.45, 46 This variant accounts for approximately two-fold changes Alvelestat clinical trial in ABCB1 messenger RNA expression in liver tissue in vitro.47 In the Mexican American population studied here, individuals with one or two copies of T allele are less prone to HAV infection, suggesting that ABCB1 rs1045642 may affect the individual’s susceptibility to HAV infection via the protective effect of ABCB1 in liver during viral hepatitis. Serologic evidence of hepatitis A infection was more prevalent among Mexican Americans (71.5%) compared with non-Hispanic whites (24.9%) and blacks (39.2%). Hepatitis A is endemic in Mexico and in Central and South Selleckchem NVP-AUY922 America.48 The higher infection prevalence and hepatitis A incidence in Hispanic communities may be due to more opportunities

for exposure arising from higher

levels of circulating virus in the community or more frequent travel to HAV-endemic countries. Host genetic variation may explain, at least in part, the marked increase in the prevalence of HAV infection in Mexican Americans compared with other racial/ethnic groups. It is striking that the high seroprevalence of HAV infection in Mexican Americans displayed such close associations with high frequencies of the TGFB1, ABCB1, and XRCC1 functional alleles. Alternatively, these differences in the loci found associated with HAV infection across racial/ethnic groups may be caused by varying linkage MCE公司 disequilibrium patterns (Supporting Fig. 1) or by gene-environment interactions that have not been identified or measured.49, 50 While the genetic associations observed from this large population-based survey may be representative and generalizable to the United States population, there are several limitations to discuss. Overly conservative P values may be generated by FDR, which may decrease our ability to identify true associations. Unlike unadjusted P values expressing the probability of a false-positive result for a single test, the FDR gives a conservative estimate of the proportion of false-positives among variants with significant association.29 Also, this study is prone to potential confounding from population substructure, though we stratified all analyses according to self-reported race/ethnicity.