Several Different Lactase Persistence Associated Alleles and High Diversity of the Lactase Gene in the Admixed Brazilian Population

Adult-type hypolactasia is a common phenotype caused by the lactase enzyme deficiency. The −13910 C>T polymorphism, located 14 Kb upstream of the lactase gene (LCT) in the MCM6 gene was associated with lactase persistence (LP) in Europeans. This polymorphism is rare in Africa but several other variants associated with lactase persistence were observed in Africans. The aims of this study were to identify polymorphisms in the MCM6 region associated with the lactase persistence phenotype and to determine the distribution of LCT gene haplotypes in 981 individuals from North, Northeast and South Brazil. These polymorphisms were genotyped by PCR based methods and sequencing. The −13779*C,−13910*T, −13937*A, −14010*C, −14011*T LP alleles previously described in the MCM6 gene region that acts as an enhancer for the LCT gene were identified in Brazilians. The most common LP allele was −13910*T. Its frequency was highly correlated with European ancestry in the Brazilian populations investigated. The −13910*T was higher (0.295) in southern Brazilians of European ancestry and lower (0.175) in the Northern admixed population. LCT haplotypes were derived from the 10 LCT SNPs genotyped. Overall twenty six haplotypes previously described were identified in the four Brazilian populations studied. The Multidimensional Scaling analysis showed that Belém, in the north, was closer to Amerindians. Northeastern and southern Afro-descendants were more related with Bantu-speaking South Africans whereas the Southern population with European ancestry grouped with Southern and Northern Europeans. This study shows a high variability considering the number of LCT haplotypes observed. Due to the highly admixed nature of the Brazilian populations, the diagnosis of hypolactasia in Brazil, based only in the investigation of the −13910*T allele is an oversimplification.

成人型乳糖不耐受是一种由乳糖酶缺乏引发的常见表型。位于MCM6基因内、乳糖酶基因（LCT）上游14kb处的−13910 C>T多态性与欧洲人群的乳糖耐受（LP）表型相关。该多态性在非洲人群中极为罕见，但非洲人群中已发现多种其他与乳糖耐受相关的变异位点。本研究旨在鉴定与乳糖耐受表型相关的MCM6基因区域多态性，并明确巴西北部、东北部及南部共981名个体的LCT基因单倍型分布情况。上述多态性通过基于聚合酶链式反应（PCR）的方法及测序技术完成基因分型。研究人员在巴西人群中鉴定出此前已在作为LCT基因增强子的MCM6基因区域中报道的−13779*C、−13910*T、−13937*A、−14010*C、−14011*T等乳糖耐受等位基因。其中最常见的乳糖耐受等位基因为−13910*T，其频率与本次研究中巴西人群的欧洲祖先血统占比呈高度相关。该等位基因在具有欧洲血统的巴西南部人群中频率最高（0.295），而在北部混合血统人群中最低（0.175）。LCT基因单倍型由10个已完成基因分型的LCT单核苷酸多态性（SNP）位点推导而来。在本次研究的4个巴西人群中共鉴定出26种此前已有报道的单倍型。多维尺度分析结果显示，巴西北部的贝伦市人群与美洲原住民更为接近；东北部及南部的非裔后裔人群与使用班图语的南非人群亲缘关系更近，而具有欧洲血统的南部人群则与南欧及北欧人群聚类在一起。本研究结果表明，就观测到的LCT基因单倍型数量而言，巴西人群的遗传多样性较高。由于巴西人群具有高度混合的血统特征，仅通过检测−13910*T等位基因来诊断巴西人群的乳糖不耐受，未免过于简化。