脂联素基因变异决定了亚洲女性在食用高饱和脂肪、低碳水化合物饮食时对胰岛素抵抗的易感性更高。

Perilipin gene variation determines higher susceptibility to insulin resistance in Asian women when consuming a high-saturated fat, low-carbohydrate diet.

作者信息

Corella Dolores, Qi Lu, Tai E Shyong, Deurenberg-Yap Mabel, Tan Chee Eng, Chew Suok Kai, Ordovas Jose M

机构信息

Nutrition and Genomics Laboratory, JM-USDA-HNRCA at Tufts University, 711 Washington St., Boston, MA 02111, USA.

出版信息

Diabetes Care. 2006 Jun;29(6):1313-9. doi: 10.2337/dc06-0045.

DOI:10.2337/dc06-0045

PMID:16732014

Abstract

OBJECTIVE

To investigate the association between genetic variation in the adipocyte protein perilipin (PLIN) and insulin resistance in an Asian population as well as to examine their modulation by macronutrient intake.

RESEARCH DESIGN AND METHODS

A nationally representative sample (Chinese, Malays, and Indians) was selected in the Singapore National Health Survey following the World Health Organization-recommended model for field surveys of diabetes. A total of 1,909 men and 2,198 women (aged 18-69 years) were studied. Genetic (PLIN 11482G-->A and 14995A-->T), lifestyle, clinical, and biochemical data were obtained. Homeostasis model assessment of insulin resistance (HOMA-IR) was used to evaluate insulin resistance. Diet was measured by a validated food frequency questionnaire in one of every two subjects.

RESULTS

We did not find a significant between-genotype difference in insulin resistance measures. However, in women we found statistically significant gene-diet interactions (recessive model) between PLIN 11482G-->A/14995A-->T polymorphisms (in high linkage disequilibrium) and saturated fatty acids (SFAs; P = 0.003/0.005) and carbohydrate (P = 0.004/0.012) in determining HOMA-IR. These interactions were in opposite directions and were more significant for 11482G-->A, considered the tag polymorphism. Thus, women in the highest SFA tertile (11.8-19%) had higher HOMA-IR (48% increase; P trend = 0.006) than women in the lowest (3.1-9.4%) only if they were homozygotes for the PLIN minor allele. Conversely, HOMA-IR decreased (-24%; P trend = 0.046) as carbohydrate intake increased. These effects were stronger when SFAs and carbohydrate were combined as an SFA-to-carbohydrate ratio. Moreover, this gene-diet interaction was homogeneously found across the three ethnic groups.

CONCLUSIONS

PLIN 11482G-->A/14995A-->T polymorphisms modulate the association between SFAs/carbohydrate in diet and insulin resistance in Asian women.

摘要

目的

研究亚洲人群中脂肪细胞蛋白围脂滴蛋白（PLIN）的基因变异与胰岛素抵抗之间的关联，并探讨常量营养素摄入对其的调节作用。

研究设计与方法

按照世界卫生组织推荐的糖尿病现场调查模型，在新加坡全国健康调查中选取了具有全国代表性的样本（华人、马来人和印度人）。共研究了1909名男性和2198名女性（年龄在18 - 69岁之间）。获取了基因（PLIN 11482G→A和14995A→T）、生活方式、临床和生化数据。采用胰岛素抵抗的稳态模型评估（HOMA-IR）来评估胰岛素抵抗。每两名受试者中就有一人通过经过验证的食物频率问卷来测量饮食情况。

结果

我们未发现胰岛素抵抗测量指标在基因型之间存在显著差异。然而，在女性中，我们发现PLIN 11482G→A/14995A→T多态性（处于高度连锁不平衡状态）与饱和脂肪酸（SFA；P = 0.003/0.005）和碳水化合物（P = 0.004/0.012）在决定HOMA-IR方面存在统计学上显著的基因 - 饮食相互作用（隐性模型）。这些相互作用方向相反，对于被视为标签多态性的11482G→A更为显著。因此，只有当PLIN次要等位基因纯合时，处于最高SFA三分位数（11.8 - 19%）的女性比处于最低三分位数（3.1 - 9.4%）的女性具有更高的HOMA-IR（增加48%；P趋势 = 0.006）。相反，随着碳水化合物摄入量增加，HOMA-IR降低（-24%；P趋势 = 0.046）。当将SFA和碳水化合物合并为SFA与碳水化合物的比例时，这些效应更强。此外，在这三个种族群体中均一致发现了这种基因 - 饮食相互作用。