A novel polymorphism associated with lactose tolerance in Africa: multiple causes for lactase persistence?
A novel polymorphism associated with lactose tolerance in Africa: multiple causes for lactase persistence?
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DOI：
10.1007/s00439-006-0291-1
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发表时间：
2007-01-01
期刊：
影响因子：
5.3
通讯作者：
Swallow, Dallas M.
中科院分区：
文献类型：
--
作者：
Ingram, Catherine J. E.;Elamin, Mohamed F.;Swallow, Dallas M.
乳糖酶在成年后表达的持久性或非持久性是一种多态性状，其原因是乳糖酶基因（LCT）上游13.9 kb增强子元件中的单核苷酸多态性（C-13910T）。-13910*T等位基因作为长单倍型（称为a）的一部分，在北欧人中出现的频率很高，并促进转录因子Oct-1的结合。然而，-13910*T在非洲许多饮用牛奶的牧民群体中出现的频率非常低，而据报道，乳糖酶持久性表型的频率很高。我们首次报道了一项对乳糖消化者和非乳糖消化者苏丹志愿者的队列研究，结果表明-13910*T或a单倍型与乳糖酶持久性没有关联。我们通过对来自东非和中东的游牧群体进行新的基因型/表型频率比较来支持这一发现。重测序发现3个新的snp靠近-13910*T，其中2个位于Oct-1结合位点。其中最常见的（-13915*G）在队列研究中与乳糖耐受性有关，为顺式作用效应提供了证据。尽管它的位置，-13915*G消除而不是增强Oct-1结合，表明这种特殊的相互作用不太可能参与乳糖酶的持久性。这项研究揭示了这种表型多态性的复杂性，并强调了C-13910T作为乳糖酶持续状态诊断测试的局限性，至少对于非欧洲血统的人来说是如此。
Persistence or non-persistence of lactase expression into adult life is a polymorphic trait that has been attributed to a single nucleotide polymorphism (C-13910T) in an enhancer element 13.9 kb upstream of the lactase gene (LCT). The -13910*T allele occurs at very high frequency in northern Europeans as part of a very long haplotype (known as A), and promotes binding of the transcription factor Oct-1. However, -13910*T is at very low frequency in many African milk drinking pastoralist groups where lactase persistence phenotype has been reported at high frequency. We report here for the first time, a cohort study of lactose digester and non-digester Sudanese volunteers and show there is no association of -13910*T or the A haplotype with lactase persistence. We support this finding with new genotype/phenotype frequency comparisons in pastoralist groups of eastern African and Middle Eastern origin. Resequencing revealed three new SNPs in close proximity to -13910*T, two of which are within the Oct-1 binding site. The most frequent of these (-13915*G) is associated with lactose tolerance in the cohort study, providing evidence for a cis-acting effect. Despite its location, -13915*G abolishes, rather than enhances Oct-1 binding, indicating that this particular interaction is unlikely to be involved in lactase persistence. This study reveals the complexity of this phenotypic polymorphism and highlights the limitations of C-13910T as a diagnostic test for lactase persistence status, at least for people with non-European ancestry.