Selection Variability for Arg48His in Alcohol DehydrogenaseADH1BAmong Asian Populations

Abstract

The variant His at codon 48 of the alcohol dehydrogenase gene (ADH1B) results in more efficient ethanol metabolism than with the "typical" codon 48Arg. In this study we introduced selection properties of Arg48His genotypes of ADH1B and estimated fitness in four ethnic-geographical clusters in Asia. Population genetics models were employed that derive observed gene frequencies from fitness relationships among genotypes, to infer the selection pattern of polymorphisms in an indirect manner. The data were analyzed using the model of "complete stationary distribution" by Wright that takes into account random genetic drift, pressure of migrations, mutations, and selection as influential factors of gene frequency. We found that the different population groups showed some variation in the types of selection for Arg48His. Han Chinese from eastern and southeastern China and the Japanese and Korean populations showed stabilizing selection, while the groups from Central Asian and Indochina showed divergent selection. However, all the groups demonstrated a strong positive selection for Arg48His.

ADH1B: From alcoholism, natural selection, and cancer to the human phenome

“…Methods based to different selection statistics (e.g., population differentiation and haplotype lengths) were applied to genome-wide data and confirmed the positive selection signatures in ADH1B gene in Asians [Peter and others 2012; Wang and others 2014c]. Some authors also hypothesized that, within Asian ancestry, other types of natural selection for ADH1B rs1229984, together with positive selection, are also present, including stabilizing selection and divergent selection [Evsyukov and Ivanov 2013]. A recent investigation based on principal component analysis also reported a genome-wide significant signal of selection for ADH1B locus in Europeans, suggesting convergent evolution in Europe and East Asia [Galinsky and others 2016].…”

Recent Selection on a Class I ADH Locus Distinguishes Southwest Asian Populations Including Ashkenazi Jews

“…The protective effect against alcoholism of the ADH1B*48His (previously named ADH2*2 ) allele at rs1229984 is considered one of the most strongly confirmed associations [ 1 , 9 , 10 , 11 , 12 ]. Also strongly confirmed is the evidence that the derived-protective allele ( ADH1B*48His ) has undergone recent positive selection in East Asia [ 13 , 14 , 15 , 16 , 17 ]. Different geographic regions differ in the frequencies of the genetic polymorphisms in ADH1B and ADH1C , the genes for the primary ethanol metabolizing enzymes [ 18 , 19 ].…”