High prevalence of an anti-hypertriglyceridemic variant of the MLXIPL gene in Central Asia
High prevalence of an anti-hypertriglyceridemic variant of the MLXIPL gene in Central Asia
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DOI：
10.1038/jhg.2011.109
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发表时间：
2011-12-01
影响因子：
3.5
通讯作者：
Iwamoto, Sadahiko
中科院分区：
文献类型：
--
作者：
Nakayama, Kazuhiro;Yanagisawa, Yoshiko;Iwamoto, Sadahiko
MLXIPL是调节肝脏糖酵解和脂肪生成不可或缺的转录因子。已知MLXIPL基因（MLXIPL）的常见变体会影响欧洲血统人群的血浆甘油三酯水平。由于MLXIPL在能量储存中发挥关键作用，MLXIPL的遗传变异可能与现代人类进化过程中发生的营养应激的生理适应有关。在本研究中，我们评估了MLXIPL Q241 H变异体在亚洲和大洋洲人群中的表型后果，并调查了Q241 H变异体在全球人群中的患病率。基于2373例亚裔个体的多元线性回归模型显示，H等位基因与血浆甘油三酯浓度降低显著相关（P=0.0003）。对来自非洲、亚洲和大洋洲的1455名个体进行的直接基因分型表明，在大多数受检人群中，降胆固醇H等位基因的频率很低（0.00-0.16）。一些中亚人群，包括蒙古族、藏族和维吾尔族，H等位基因的频率要高得多（0.21-0.26）。H等位基因在中亚的高患病率意味着MLXIPL的Q241 H变体可能对这些人群的共同祖先利用碳水化合物和脂肪具有重要意义，这些人群通过依靠游牧牲畜放牧成功适应了中亚的环境。Journal of Human Genetics（2011）56，828-833; doi：10.1038/jhg.2011.109; 2011年9月22日在线发表
MLXIPL is a transcription factor integral to the regulation of glycolysis and lipogenesis in the liver. Common variants of the MLXIPL gene (MLXIPL) are known to influence plasma triglyceride levels in people of European descent. As MLXIPL has a key role in energy storage, genetic variations of the MLXIPL may be relevant to physiological adaptations to nutritional stresses that have occurred during the evolution of modern humans. In the present study, we assessed the phenotypic consequences of the Q241H variant of MLXIPL in populations of Asian and Oceanian origin and also surveyed the prevalence of Q241H variant in populations worldwide. Multiple linear regression models based on 2373 individuals of Asian origin showed that the H allele was significantly associated with decreased concentrations of plasma triglycerides (P=0.0003). Direct genotyping of 1455 individuals from Africa, Asia and Oceania showed that the triglyceride-lowering H allele was found at quite low frequencies (0.00-0.16) in most of the populations examined. The exceptions were some Central Asian populations, including Mongolians, Tibetans and Uyghurs, which exhibited much higher frequencies of the H allele (0.21-0.26). The high prevalence of the H allele in Central Asia implies that the Q241H variant of MLXIPL might have been significant for utilization of carbohydrates and fats in the common ancestors of these populations, who successfully adapted to the environment of Central Asia by relying on nomadic livestock herding. Journal of Human Genetics (2011) 56, 828-833; doi:10.1038/jhg.2011.109; published online 22 September 2011