Differential Association of Niemann-Pick C1 Gene Polymorphisms with Maternal Prepregnancy Overweight and Gestational Diabetes.

William S Garver, Lesley de la Torre, Matthew C Brennan, Li Luo, David Jelinek, Joseph J Castillo, David Meyre, Robert A Orlando, Randall A Heidenreich, William F Rayburn
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引用次数: 3

Abstract

A genome-wide association study (GWAS) and subsequent replication studies in diverse ethnic groups indicate that common Niemann-Pick C1 gene (NPC1) polymorphisms are associated with morbid-adult obesity or diabetes independent of body weight. The objectives for this prospective cross-sectional study were to determine allele frequencies for NPC1 polymorphisms (644A>G, 1926C>G, 2572A>G, and 3797G>A) and association with metabolic disease phenotypes in an ethnically diverse New Mexican obstetric population. Allele frequencies for 1926C>G, 2572A>G, and 3797G>A were significantly different between race/ethnic groups (non-Hispanic white, Hispanic, and Native American). The results also indicated a significant pairwise linkage-disequilibrium between each of the four NPC1 polymorphisms in race/ethnic groups. Moreover, the derived and major allele for 1926C>G was associated (OR 2.11, 95% CI 1.10-3.96, P = 0.022) with increased risk for maternal prepregnancy overweight (BMI 25.0-29.9kg/m2) while the ancestral and major allele for 2572A>G was associated (OR 4.68, 95% CI 1.23-17.8, P = 0.024) with increased risk for gestational diabetes in non-Hispanic whites, but not Hispanics or Native Americans. In summary, this is the first transferability study to investigate common NPC1 polymorphisms in a multiethnic population and demonstrate a differential association with increased risk for maternal prepregnancy overweight and gestational diabetes.

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尼曼-匹克C1基因多态性与孕妇孕前超重和妊娠期糖尿病的差异关联
一项全基因组关联研究(GWAS)和随后在不同种族群体中的复制研究表明,常见的尼曼-匹克C1基因(NPC1)多态性与体重无关的成人肥胖或糖尿病有关。这项前瞻性横断面研究的目的是确定NPC1多态性(644A>G、1926C>G、2572A>G和3797G>A)的等位基因频率及其与新墨西哥不同种族产科人群代谢性疾病表型的关系。1926C>G、2572A>G和3797G>A的等位基因频率在不同种族/民族(非西班牙裔白人、西班牙裔和美洲原住民)之间存在显著差异。结果还表明,四种NPC1多态性在种族/民族群体中存在显著的成对连锁不平衡。此外,1926C>G的衍生和主要等位基因与孕妇孕前超重(BMI 25.0-29.9kg/m2)的风险增加相关(OR 2.11, 95% CI 1.10-3.96, P = 0.022),而2572A>G的祖先和主要等位基因与非西班牙裔白人妊娠糖尿病风险增加相关(OR 4.68, 95% CI 1.23-17.8, P = 0.024),但与西班牙裔或美洲原住民无关。总之,这是第一个在多种族人群中调查常见NPC1多态性的可转移性研究,并证明了NPC1多态性与孕妇孕前超重和妊娠糖尿病风险增加的差异关联。
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