Tracing the Distribution of European Lactase Persistence Genotypes Along the Americas

Abstract

In adulthood, the ability to digest lactose, the main sugar present in milk of mammals, is a phenotype (lactase persistence) observed in historically herder populations, mainly Northern Europeans, Eastern Africans, and Middle Eastern nomads. As the –13910∗T allele in the MCM6 gene is the most well-characterized allele responsible for the lactase persistence phenotype, the –13910C > T (rs4988235) polymorphism is commonly evaluated in lactase persistence studies. Lactase non-persistent adults may develop symptoms of lactose intolerance when consuming dairy products. In the Americas, there is no evidence of the consumption of these products until the arrival of Europeans. However, several American countries’ dietary guidelines recommend consuming dairy for adequate human nutrition and health promotion. Considering the extensive use of dairy and the complex ancestry of Pan-American admixed populations, we studied the distribution of –13910C > T lactase persistence genotypes and its flanking haplotypes of European origin in 7,428 individuals from several Pan-American admixed populations. We found that the –13910∗T allele frequency in Pan-American admixed populations is directly correlated with allele frequency of the European sources. Moreover, we did not observe any overrepresentation of European haplotypes in the –13910C > T flanking region, suggesting no selective pressure after admixture in the Americas. Finally, considering the dominant effect of the –13910∗T allele, our results indicate that Pan-American admixed populations are likely to have higher frequency of lactose intolerance, suggesting that general dietary guidelines deserve further evaluation across the continent.

DNA polymorphisms associated with lactase persistence, self‐perceived symptoms of lactose intolerance, milk and dairy consumption, and ancestry, in the Uruguayan population

“…The Arab variant G‐13915 and the rare allele T‐14011, both found in Tacuarembó with an allelic frequency of 0.4%, were previously reported at very low frequencies in Brazilians (Friedrich, Santos, et al, 2012; Guimarães Alves et al, 2021), while the first one was also reported in Ecuadorians (Paz y Miño et al, 2016). Variant G‐13915 exhibits it highest frequency in Saudi Arabia (57%), with minor frequencies in other Middle East Arabs, North Africa, and East Africa (Table A1).…”

“…Particularly, we have estimated in the population of Tacuarembó a mean of 80.4% of European contribution based on nDNA, and previously Bonilla et al (2015) had estimated a mean of 77.1% for the whole country. Recently, Guimarães Alves et al (2021) estimated 83.4% of European ancestry proportion for a sample of Uruguay, and reported a frequency of the LP associated allele (T‐13910) of 35.3% in Uruguay, the highest among the American populations they have analyzed. Similar frequencies of T‐13910 were reported in Euro‐Brazilians from southern Brazil, while in other South American cosmopolitan populations, with smaller European contributions, T‐13910 allele frequency ranged from 10% to 22%.…”

“…Several studies carried out in admixed, African and Native American populations of south America have shown that the frequency of the T‐13910 allele is markedly associated with the proportion of European ancestry in the population (Fernández et al, 2016; Fernández & Flores, 2014; Friedrich, Callegari‐Jacques, et al, 2012; Friedrich, Santos, et al, 2012; Guimarães Alves et al, 2021; Mattar et al, 2009; Paz y Miño et al, 2016). In our study, we wanted to explore if C/T‐13910 genotype and genetic biparental and maternal ancestry were statistically associated within the population of Tacuarembó.…”

“…In this context, diverse studies carried out in Brazil, Ecuador, Colombia, Peru, and Chile found the C/T‐13910 SNP to be the most frequent polymorphism associated with LP. However, T‐13910 allele frequency varies greatly depending on ethnic affiliation or genetic ancestry background of the population or individuals studied, being higher when European contribution increases (Fernández & Flores, 2014; Friedrich, Santos, et al, 2012; Guimarães Alves et al, 2021; Mattar et al, 2009; Mendoza Torres et al, 2012; Paz y Miño et al, 2016). Association between expected lactose digestion phenotype considering C/T‐13910 genotype, and the effectively observed phenotype, was assessed in some studies in South America.…”

“…Furthermore, they found significant differences in percentages of LNP and LI when “white” and “black” participants were compared. Recently, Guimarães Alves et al (2021) reported in a sample of 191 Uruguayans a frequency of the derived T‐13910 allele of 35%, and a proportion of LP phenotype, considering T‐13910 carriers, of 61%.…”