Genetic anthropology of the blood lipid level

为了阐明人类血脂水平遗传变异的人类学意义，对来自5个亚洲和大洋洲人群的2万多人进行了血脂相关基因的常见和罕见变异调查。1)脂肪酸去饱和酶（FADS）基因变异对血脂水平的影响在蒙古人和日本人之间存在显著差异。膳食中不饱和脂肪酸摄入量的差异可以解释FADS基因变异的表型效应差异。2)抗高甘油三酯血症MLXIPL gln241他的变体在中亚人中发现频率很高，可以追溯到游牧牧民。他的变异可能对游牧牧民对碳水化合物和脂肪的利用具有重要意义。3)清道夫受体B类基因家族重测序显示泰国个体中存在过量的罕见变异。这表明脂质代谢的遗传变异与疟疾抗性之间可能存在联系。4)此外，本研究表明，在血脂水平的关联研究中，调整内脏脂肪积累可以提高遗传变异检测效果的敏感性。

To elucidate anthropological significance of genetic variation for blood lipid level in humans, over 20,000 individuals from 5 Asian and Oceanian groups were investigated for common and rare variants of lipid associated genes. 1) Effects of FADS (fatty acid desaturase) gene variants on blood lipid level were dramatically varied between Mongolians and Japanese. Differences in dietary intake of unsaturated fatty acid would explain the variation in phenotypic effects of the FADS gene variants. 2) Anti-hypertriglyceridemic MLXIPL Gln241His variant was found with high frequencies in central Asians who can be traced back to nomadic pastoralists. Gln241His variant might have been significant for utilization of carbohydrates and fats in nomadic pastoralists. 3) Resequencing of Scavenger receptor class B gene family revealed excess of rare variants among Thai individuals. This suggested a possible link between genetic variation of lipid metabolism and malaria resistance. 4) Additionally, the present study showed that in an association study of blood lipid level, adjustment for visceral fat accumulation can improve sensitivity of detecting effects of genetic variants.