女性基因组健康研究中体脂和遗传因素与甘油三酯和富含甘油三酯的脂蛋白的关系。
Adiposity and Genetic Factors in Relation to Triglycerides and Triglyceride-Rich Lipoproteins in the Women's Genome Health Study.
机构信息
Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA;
Preventive Medicine Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
出版信息
Clin Chem. 2018 Jan;64(1):231-241. doi: 10.1373/clinchem.2017.280545. Epub 2017 Nov 2.
BACKGROUND
Previous results from Scandinavian cohorts have shown that obesity accentuates the effects of common genetic susceptibility variants on increased triglycerides (TG). Whether such interactions are present in the US population and further selective for particular TG-rich lipoprotein subfractions is unknown.
METHODS
We examined these questions using body mass index (BMI) and waist circumference (WC) among women of European ancestry from the Women's Genome Health Study (WGHS) (n = 21840 for BMI; n = 19313 for WC). A weighted genetic risk score (TG-wGRS) based on 40 published TG-associated single-nucleotide polymorphisms was calculated using published effect estimates.
RESULTS
Comparing overweight (BMI ≥ 25 kg/m) and normal weight (BMI < 25 kg/m) WGHS women, each unit increase of TG-wGRS was associated with TG increases of 1.013% and 1.011%, respectively, and this differential association was significant ( = 0.014). Metaanalyses combining results for WGHS BMI with the 4 Scandinavian cohorts (INTER99, HEALTH2006, GLACIER, MDC) (total n = 40026) yielded a more significant interaction ( = 0.001). Similarly, we observed differential association of the TG-wGRS with TG ( = 0.006) in strata of WC (<80 cm vs ≥80 cm). Metaanalysis with 2 additional cohorts reporting WC (INTER99 and HEALTH2006) (total n = 27834) was significant with consistent effects ( = 0.006). We also observed highly significant interactions of the TG-wGRS across the strata of BMI with very large, medium, and small TG-rich lipoprotein subfractions measured by nuclear magnetic resonance spectroscopy (all < 0.0001). The differential effects were strongest for very large TG-rich lipoprotein.
CONCLUSIONS
Our results support the original findings and suggest that obese individuals may be more susceptible to aggregated genetic risk associated with common TG-raising alleles, with effects accentuated in the large TG-rich lipoprotein subfraction.
背景
斯堪的纳维亚队列的先前研究结果表明，肥胖会加剧常见遗传易感变异对甘油三酯（TG）升高的影响。在美国人群中是否存在这种相互作用，以及是否对特定富含 TG 的脂蛋白亚组分具有选择性，目前尚不清楚。
方法
我们使用欧洲裔女性的体重指数（BMI）和腰围（WC）（BMI 为 21840 人；WC 为 19313 人），在女性基因组健康研究（WGHS）中检验了这些问题。使用已发表的效应估计值，基于 40 个已发表的与 TG 相关的单核苷酸多态性，计算了一个基于 TG 的加权遗传风险评分（TG-wGRS）。
结果
在超重（BMI≥25kg/m2）和正常体重（BMI<25kg/m2）的 WGHS 女性中，TG-wGRS 每增加一个单位，分别与 TG 增加 1.013%和 1.011%相关，这种差异关联具有统计学意义（=0.014）。对 WGHS BMI 与 4 个斯堪的纳维亚队列（INTER99、HEALTH2006、GLACIER、MDC）（共 40026 人）的结果进行的荟萃分析产生了一个更显著的交互作用（=0.001）。同样，我们观察到 TG-wGRS 与 TG 的关联在 WC 分层（<80cm 与≥80cm）中存在差异（=0.006）。对另外两个报告 WC 的队列（INTER99 和 HEALTH2006）（共 27834 人）进行的荟萃分析具有统计学意义，并且效应一致（=0.006）。我们还观察到，TG-wGRS 与通过核磁共振光谱测量的富含 TG 的小、中、大脂蛋白亚组分的 BMI 分层之间存在高度显著的相互作用（均<0.0001）。对于非常大的富含 TG 的脂蛋白，差异效应最强。
结论
我们的结果支持最初的发现，并表明肥胖个体可能更容易受到与常见升高 TG 的等位基因相关的聚集遗传风险的影响，并且在富含 TG 的大脂蛋白亚组分中，这种影响更加明显。
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