Chandalia Manisha, Grundy Scott M, Adams-Huet Beverley, Abate Nicola
Division of Endocrinology and Metabolism and The Center for Human Nutrition, Department of Medicine, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390-9169, USA.
J Diabetes Complications. 2007 May-Jun;21(3):143-8. doi: 10.1016/j.jdiacomp.2006.11.003.
Genetic susceptibility modulates the impact of obesity on the risk for type 2 diabetes. One candidate gene predisposing to type 2 diabetes is ENPP1/PC1. A common polymorphism in this protein, K121Q, is associated with insulin resistance and increased susceptibility to type 2 diabetes in Caucasian, Afro-Caribbean, and South Asian populations. The goal of this study was to evaluate differences in the prevalence of the ENPP1 121Q variant in the Caucasian, African-American, and Hispanic populations in Dallas county and to establish a population-based estimate of gene variant prevalence for future investigations. We also evaluated the association between the ENPP1 121Q variant and diabetes. The Dallas Heart Study (DHS) is a multiethnic probability-based sample of the Dallas county population in which African-Americans were systematically oversampled so that the final sample was 50% African-Americans. We performed ENPP1/PC1 genotyping in 1038 non-Hispanic Whites (544 women, 494 men), 1815 African-Americans (1052 women and 763 men), and 597 Hispanics (347 women, 250 men). The frequency of ENPP1/PC1 K121Q was higher in both African-Americans (78.5%) and Hispanics (21.9%) than in the non-Hispanic White group (13.2%). The former two groups also have a higher prevalence of type 2 diabetes (African-Americans, 14.1%, and Hispanics, 11.7%) compared to non-Hispanic Whites (6.8%). Logistic regression analysis revealed significant interactions between the ENPP1 genotype, age, and body mass index within each ethnic group. After adjustment for these variables and their interactions, ENPP1 Q allele predicted diabetes when a recessive model was tested. Ethnic differences in ENPP1 121Q allele frequency may contribute to the increased susceptibility to type 2 diabetes observed in US minority groups.
遗传易感性调节肥胖对2型糖尿病风险的影响。一种与2型糖尿病易感性相关的候选基因是ENPP1/PC1。该蛋白中的一种常见多态性K121Q，与白种人、非裔加勒比人和南亚人群的胰岛素抵抗及2型糖尿病易感性增加有关。本研究的目的是评估达拉斯县白种人、非裔美国人和西班牙裔人群中ENPP1 121Q变异体的患病率差异，并为未来研究建立基于人群的基因变异体患病率估计值。我们还评估了ENPP1 121Q变异体与糖尿病之间的关联。达拉斯心脏研究（DHS）是基于概率的达拉斯县多民族样本，其中非裔美国人被系统地过度抽样，以便最终样本中50%是非裔美国人。我们对1038名非西班牙裔白人（544名女性，494名男性）、1815名非裔美国人（1052名女性和763名男性）和597名西班牙裔（347名女性，250名男性）进行了ENPP1/PC1基因分型。ENPP1/PC1 K121Q的频率在非裔美国人（78.5%）和西班牙裔（21.9%）中均高于非西班牙裔白人组（13.2%）。与非西班牙裔白人（6.8%）相比，前两组2型糖尿病的患病率也更高（非裔美国人，14.1%；西班牙裔，11.7%）。逻辑回归分析显示，每个种族群体中ENPP1基因型、年龄和体重指数之间存在显著相互作用。在对这些变量及其相互作用进行调整后，当测试隐性模型时，ENPP1 Q等位基因可预测糖尿病。ENPP1 121Q等位基因频率的种族差异可能导致美国少数群体中观察到的2型糖尿病易感性增加。
