Apolipoprotein E/C1/C4/C2 Gene Cluster Diversity in Two Native Andean Populations: Aymaras and Quechuas

Abstract

SummaryThe APOE/C1/C4/C2 gene cluster presents high relevance in lipid metabolism and, therefore, has important epidemiological implications. Here, we study for the first time the variation patterns of 25 polymorphisms (10 short tandem repeats, STRs, and 15 single nucleotide polymorphismas, SNPs) in two native Andean samples from Bolivia (45 Aymaras and 45 Quechuas) as well as one European sample (n = 41) as external reference. We estimated diversity parameters, linkage disequilibrium patterns, population structure, and possible selective effects. In general, diversity was low and could be partly attributed to selection (probably due to its physiological importance), since the APOE/C1/C4/C2 region was highly conserved compared to the flanking genes in both Bolivians and Europeans. Moreover, the lower gene diversity in Bolivians compared to Europeans for some markers might indicate different demographic histories. Regarding the APOE isoforms, in addition to ε3 (94%) and ε4 (5%), isoform ε2 (1%) was also detected in Bolivians. In relation to previous hypotheses, our results support that genetic drift or founder effects rather than selection for increased cholesterol absorption are the main factors that have shaped the distribution of APOE isoforms observed in South America.

APOE4 is associated with elevated blood lipids and lower levels of innate immune biomarkers in a tropical Amerindian subsistence population

“…Finally, nearly one-fourth of individuals in the sample had at least one copy of APOE4 . The allelic frequency of APOE4 reported here is similar to what has been previously documented among other South American and Amerindian populations, which ranges from 5% to 30% and varies widely by region and level of genetic admixture ( Corbo and Scacchi, 1999 ; Gayà-Vidal et al, 2012 ). The distribution of APOE allelic variants in populations around the world is likely due to a mosaic of factors, from genetic drift, to antagonistic pleiotropy, to potential differences related to environmentally dependent costs and benefits of functionally distinct variants.…”

“…The distribution of APOE allelic variants in populations around the world is likely due to a mosaic of factors, from genetic drift, to antagonistic pleiotropy, to potential differences related to environmentally dependent costs and benefits of functionally distinct variants. Certainly some degree of genetic drift or founder effects ( Gayà-Vidal et al, 2012 ; Singh et al, 2006 ), antagonistic pleiotropy ( Smith et al, 2019 ; van Exel et al, 2017 ) and other forces (e.g. genetic relatedness) play an important role in determining population and global frequencies and should be considered jointly to make inferences about the frequency of E4 in the Tsimane population.…”

Global genetic diversity of human apolipoproteins and effects on cardiovascular disease risk

“… AD, Alzheimer’s disease; AFR, Africans; AJ, Ashkenazi Jews; AMR, Latinos; CAC, coronary artery calcification; CHD, coronary heart disease; EAS, East Asians; EUR, Europeans; HDL, HDL levels; HGVS, Human Genome Variation Society; HR, hazard ratio; LDL, LDL levels; LDL-C, LDL cholesterol; N.A., not available; RA, rheumatoid arthritis; RSID, reference SNP cluster ID; SAS, South Asians; T2DM, T2D mellitus; TC, total cholesterol levels; TG, triglyceride levels; VLDL, VLDL levels; VT, venous thrombosis; β, standardized effect size; β′, nonstandardized effect size. a Obtained from Gayà-Vidal et al ( 97 ). b Obtained from Gao et al ( 98 ).…”

A tale of agriculturalists and hunter‐gatherers: Exploring the thrifty genotype hypothesis in native South Americans

“…Therefore, except for the Lengua population, Andoas, Apalai, Gavião, Guarani, Jamamadi, Surui, Wai‐Wai, and Zoró can be considered typical populations of the rain forest environment; and (b) Andean agriculturalists and camelid‐herding communities from Peru: Amantani ( n = 29), Anapia ( n = 15), Cabanaconde ( n = 7), Chivay ( n = 4), Taquile ( n = 41), Yanque ( n = 10), Quechua ( n = 40), and Uros ( n = 22). For comparison and sample enrichment for APOE markers, APOE genotype data from 39 Aymara individuals from Bolivia listed in Gayà‐Vidal et al, () were included in the analyses. Unlike others groups living within the same vicinity, the Uros are not classical Andean agro‐pastoralists since they traditionally live in the floating islands of Lake Titicaca.…”