Contribution of infectious diseases to the selection of ADH1B and ALDH2 gene variants in Asian populations

ADH1B型 生物 遗传学 ALDH2 等位基因频率 等位基因 人口 基因 医学 环境卫生 支链α-酮酸脱氢酶复合物 生物化学 脱氢酶
作者
Giovanni Deiana,Ruinan Sun,Jie Huang,Valerio Napolioni,Roberto Ciccocioppo
标识
DOI:10.1111/acer.15288
摘要

Abstract Background The gene variants ADH1B* 2 (Arg48His, rs1229984) and ALDH2 *2 (Glu504Lys, rs671) are common in East Asian populations but rare in other populations. We propose that selective pressures from pathogen exposure and dietary changes during the neolithic transition favored these variants. Thus, their current association with differences in alcohol sensitivity likely results from phenotypic plasticity rather than direct natural selection. Methods Samples sourced from the Allele Frequency Database (ALFRED) were utilized to compute the average frequency of ADH1B *2 and ALDH2 *2 across 88 and 61 countries, respectively. Following computation of the average national allele frequencies, we tested the significance of their correlations with ecological variables. Subsequently, we subjected them to Principal Component Analysis (PCA) and Elastic Net regularization. For comprehensive evaluation, we collected individual‐level phenotypic associations, compiling a Phenome‐Wide Association Study (PheWAS) spanning multiple ethnicities. Results Following multiple testing correction, ADH1B *2 displayed significant correlations with Neolithic transition timing ( r = 0.405, p .adj = 2.013e‐03, n = 57) and historical trypanosome burden ( r = −0.418, p .adj = 0.013, n = 57). The first two components of PCA explained 47.7% of the total variability across countries, with the top three contributors being the historical indices of population density and trypanosome and leprosy burdens. Historical burdens of the Mycobacteria tuberculosis and leprosy were the sole predictive variables with positive coefficients that survived Elastic Net regularization. Conclusions Our analyses suggest that Mycobacteria may have played a role in the joint selection of ADH1B *2 and ALDH2 *2, expanding the “toxic aldehyde hypothesis” to include Mycobacterium leprae . Additionally, our hypothesis, linked to dietary shifts from rice domestication, emphasizes nutritional deficiencies as a key element in the selective pressure exerted by Mycobacteria . This offers a plausible explanation for the high frequency of ADH1B *2 and ALDH2 *2 in Asian populations.
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