51. Differential Association of Niemann-Pick C1 Gene Polymorphisms with Maternal Prepregnancy Overweight and Gestational Diabetes
- Author
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Joseph J. Castillo, M. C. Brennan, Randall A. Heidenreich, Robert A. Orlando, William F. Rayburn, William S. Garver, David Jelinek, de la Torre L, David Meyre, and Li Luo
- Subjects
Genetics ,education.field_of_study ,business.industry ,Population ,Physiology ,Genome-wide association study ,Overweight ,medicine.disease ,Obesity ,Article ,Gestational diabetes ,Obstetrics ,Diabetes mellitus ,medicine ,Niemann-Pick C1 ,Allele ,medicine.symptom ,Polymorphism ,business ,education ,Allele frequency - 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.
- Published
- 2015