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

A genome-wide association study and later replication studies indicate that the human Niemann-Pick C1 gene (NPC1) is associated with obesity or diabetes independent of body weight. The objectives for this replication study were to determine frequencies for NPC1 polymorphisms (644A>G, 1926G>C, 2572A>G, and 3797G>A) in a diverse New Mexican obstetric population and evaluate whether these polymorphisms were associated with metabolic disease phenotypes (overweight, obesity, different forms of diabetes, HbA1c levels, and large for gestational age infants). Frequencies of certain NPC1 polymorphisms (1926G>C, 2572A>G, and 3797G>A) were significantly different between race/ethnic groups. The 2572A>G ancestral allele was associated (OR 4.94; 95% CI 3.30-5.87, P = 0.019) with gestational diabetes among non-Hispanic whites, while the derived allele was associated (OR 2.03; 95% CI 1.04-3.97, P = 0.039) with gestational diabetes among Mexican Americans. Moreover, the 1926G>C ancestral allele was associated (OR 2.02; 95% CI 1.08-3.77, P = 0.027) with overweight (BMI 25.0ï??29.9 kg/m2) among non-Hispanic whites. The results also indicated a significant pairwise linkage disequilibrium between all four NPC1 polymorphisms and no significant deviation from Hardy-Weinberg equilibrium within race/ethnic groups. In conclusion, frequencies of certain NPC1 polymorphisms were different between race/ethnic groups and the 2572A>G alleles were differentially associated with gestational diabetes.