A meta-analysis revealed that low-density lipoprotein cholesterol (LDL-C)-lowering genetic variants in or near NPC1L1 and other genes was associated with a higher risk of type 2 diabetes (T2D). The analyses included 50 775 individuals with T2D and 270 269 controls and 60 801 individuals with coronary artery disease (CAD) and 123 504 controls in Europe and the United States between 1991 and 2016. LDL-C–lowering genetic variants at NPC1L1 were inversely associated with CAD (odds ratio [OR] for a genetically predicted 1-mmol/L [38.7-mg/dL] reduction in LDL-C of 0.61) and directly associated with T2D (OR for a genetically predicted 1-mmol/L reduction in LDL-C of 2.42). For PCSK9 genetic variants, the OR for T2D per 1-mmol/L genetically predicted reduction in LDL-C was 1.19. For a given reduction in LDL-C, genetic variants were associated with a similar reduction in CAD risk. However, associations with T2D were heterogeneous, indicating gene-specific associations with metabolic risk of LDL-C-lowering alleles. Alleles near HMGCR as well as treatment with statins or niacin are known to be associated with a higher risk of T2D. The data suggest potential adverse effects of LDL-C-lowering therapy, which should be accompanied by lifestyle modification, such as appropriate diet and higher physical activity, in order to optimize risk reduction. Source: http://jamanetwork.com/
一项荟萃分析表明，位于或靠近NPC1L1和其它调降低密度脂蛋白胆固醇的基因遗传变异与2型糖尿病的风险较高有关。该分析包括欧洲和美国1991年至2016年间50 775例2型糖尿病和270 269例对照，60 801例冠心病和123 504例对照。在NPC1L1的调降低密度脂蛋白胆固醇的遗传变异与冠心病呈负相关（遗传预测1毫摩尔/升[38.7毫克/分升]低密度脂蛋白胆固醇降低的风险比为0.61），并直接与2型糖尿病相关（遗传预测1毫摩尔/升[38.7毫克/分升]低密度脂蛋白胆固醇降低的风险比为2.42）。对于PCSK9基因变异，遗传预测1毫摩尔/升[38.7毫克/分升]低密度脂蛋白胆固醇降低则2型糖尿病的风险比为1.19。对于一定程度低密度脂蛋白胆固醇的降低，与遗传变异相关的冠心病风险降低的程度亦相似。然而，2型糖尿病的相关不一致，提示调降低密度脂蛋白胆固醇的等位基因与代谢风险的关系是基因特异性的。已知邻近HMGCR的等位基因以及他汀类药物或烟酸治疗与2型糖尿病风险较高有关。这些资料提示调降低密度脂蛋白胆固醇治疗的潜在不利影响，应结合改变生活方式如适当的饮食并加强身体锻炼，以优化减少风险。来源：http://jamanetwork.com/
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