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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&gt;G, 1926C&gt;G, 2572A&gt;G, and 3797G&gt;A) and association with metabolic disease phenotypes in an ethnically diverse New Mexican obstetric population. Allele frequencies for 1926C&gt;G, 2572A&gt;G, and 3797G&gt;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&gt;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/m 2 ) while the ancestral and major allele for 2572A&gt;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.

DIFFERENTIAL ASSOCIATION OF NIEMANN-PICK C1 GENE POLYMORPHISMS WITH MATERNAL PREPREGNANCY OVERWEIGHT AND GESTATIONAL DIABETES