Association of the rs4988235(C) Polymorphism, a Determinant of Lactose Intolerance, with Genetic Ancestry in Latin American Populations
DOI:
https://doi.org/10.56294/dm2024.354Keywords:
Lactose Intolerance, rs4988235 Polymorphism, Genetic Ancestry, Latin American Populations, European Ancestry, Native-American AncestryAbstract
Introduction: the rs4988235(C) polymorphism is associated with lactose intolerance and exhibits heterogeneity among populations. In Europe, the T allele (lactose tolerance) is prevalent in the north, while the C allele (lactose intolerance) is common in Asia and Africa.
Methods: genotypes for rs4988235 were obtained from the 1000 Genomes Project database, selecting Latin American samples (Colombians, Mexican Americans, Peruvians, and Puerto Ricans). A total of 446 ancestry-informative markers (AIMs) were used to estimate genetic ancestry proportions. Shapiro-Wilks tests were conducted, and due to non-normality, non-parametric Kruskal-Wallis and post hoc Wilcoxon tests were applied.
Results: the Shapiro-Wilks test indicated significant deviations from normality for Native-American (statistic=0.8787, p<0.05) and European ancestry proportions (statistic=0.9653, p<0.05). Kruskal-Wallis analysis showed significant differences in European (statistic=26.6696, p=1.62×10−6) and Native-American (statistic=13.4306, p=0.0012) ancestry proportions among genotypes. Post hoc Wilcoxon tests indicated significant differences between Intolerant (GG) and Heterozygous (GA) genotypes for both ancestries.
Conclusions: the proportions of European and Native-American ancestry vary among genotypes of the rs4988235(C) polymorphism, suggesting the effect of admixture on the distribution of lactose intolerance in Latin American populations
References
1. Enattah NS, Sahi T, Savilahti E, Terwilliger JD, Peltonen L, Järvelä I. Identification of a variant associated with adult-type hypolactasia. Nat Genet. 2002;30(2):233-237. https://doi.org/10.1038/ng826
2. Itan Y, Powell A, Beaumont MA, Burger J, Thomas MG. The Origins of Lactase Persistence in Europe. PLoS Comput Biol. 2009;5(8). https://doi.org/10.1371/journal.pcbi.1000491
3. Ségurel L, Bon C. On the Evolution of Lactase Persistence in Humans. Annu Rev Genomics Hum Genet. 2017;18:297-319. https://doi.org/10.1146/annurev-genom-091416-035340
4. Jones BL, Raga TO, Liebert A, Zmarz P, Bekele E, Danielsen ET, Olsen AK, Bradman N, Troelsen JT, Swallow DM. Diversity of Lactase Persistence Alleles in Ethiopia: Signature of a Soft Selective Sweep. Am J Hum Genet. 2013;93(3):538-544. https://doi.org/10.1016/j.ajhg.2013.06.015
5. Anguita-Ruiz A, Aguilera CM, Gil Á. Genetics of Lactose Intolerance: An Updated Review and Online Interactive World Maps of Phenotype and Genotype Frequencies. Nutrients. 2020;12(9):2689. https://doi.org/10.3390/nu12092689
6. López S, Van Dorp L, Hellenthal G. Human dispersal out of Africa: a lasting debate. Evol Bioinform Online. 2015;11. https://doi.org/ 10.4137/EBO.S33489
7. Adhikari K, Mendoza-Revilla J, Chacón-Duque JC, Fuentes-Guajardo M, Ruiz-Linares A. Admixture in Latin America. Curr Opin Genet Dev. 2016;41:106-114. https://doi.org/ 10.1016/j.gde.2016.09.003
8. Dries DL. Genetic Ancestry, Population Admixture, and the Genetic Epidemiology of Complex Disease Editorial. Circ Cardiovasc Genet. 2009;2:540-543. https://doi.org/ 10.1161/CIRCGENETICS.109.922898
9. Creanza N, Kolodny O, Feldman MW. Cultural evolutionary theory: How culture evolves and why it matters. Proc Natl Acad Sci U S A. 2017;114(30):7782-7789. https://doi.org/10.1073/pnas.1620732114
10. Royal CD, Novembre J, Fullerton SM, Goldstein DB, Long JC, Bamshad MJ, Clark AG. Inferring genetic ancestry: opportunities, challenges, and implications. Am J Hum Genet. 2010;86(5):661-673. https://doi.org/ 10.1016/j.ajhg.2010.03.011
11. Chakraborty R. Analysis of Genetic Structure of Populations: Meaning, Methods, and Implications. In: Majumder PP, editor. Human Population Genetics. Springer; 1993. p. 191-224. https://doi.org/10.1007/978-1-4615-2970-5_14
12. Danecek P, Auton A, Abecasis G, Albers CA, Banks E, DePristo MA, et al. The variant call format and VCFtools. Bioinformatics. 2011;27(15):2156-2158. https://doi.org/ 10.1093/bioinformatics/btr330
13. 1000 Genomes Project Consortium. A global reference for human genetic variation. Nature. 2015;526(7571):68. https://doi.org/10.1038/nature15393
14. Galanter JM, Fernandez-Lopez JC, Gignoux CR, Barnholtz-Sloan J, Fernandez-Rozadilla C, Via M, et al. Development of a panel of genome-wide ancestry informative markers to study admixture throughout the Americas. PLoS Genet. 2012;8(3). https://doi.org/10.1371/journal.pgen.1002554
15. Hubisz MJ, Falush D, Stephens M, Pritchard JK. Inferring weak population structure with the assistance of sample group information. Mol Ecol Resour. 2009;9(5):1322-1332. https://doi.org/ 10.1111/j.1755-0998.2009.02591.x
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