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

Autor: Deiana G; Center for Neuroscience, Pharmacology Unit, School of Pharmacy, University of Camerino, Camerino, Italy., Sun R; Department of Public and Ecosystem Health, Cornell University College of Veterinary Medicine, Ithaca, New York, USA., Huang J; School of Public Health and Emergency Management, Southern University of Science and Technology, Shenzhen, China.; Institute for Global Health and Development, Peking University, Beijing, China., Napolioni V; School of Biosciences and Veterinary Medicine, University of Camerino, Camerino, Italy., Ciccocioppo R; Center for Neuroscience, Pharmacology Unit, School of Pharmacy, University of Camerino, Camerino, Italy.
Jazyk: angličtina
Zdroj: Alcohol, clinical & experimental research [Alcohol Clin Exp Res (Hoboken)] 2024 May; Vol. 48 (5), pp. 855-866. Date of Electronic Publication: 2024 Mar 10.
DOI: 10.1111/acer.15288
Abstrakt: 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.
(© 2024 Research Society on Alcohol.)
Databáze: MEDLINE
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