The association of a nucleobindin 2 gene (NUCB2) variant with childhood adiposity

Abstract

Nucleobindin 2 (NUCB2) is a precursor of nesfatin-1, a hypothalamic anorectic neuropeptide. The association between variants of the NUCB2 gene and adiposity was examined. 142 severely obese Chinese children in Singapore, and 384 normal weight Chinese children from a longitudinal cohort from Da Qing, China, were studied. NUCB2 was screened using PCR and direct sequencing in 29 severely obese children and 24 non-obese children, then screened for a variant c.1012C>G (Q338E, or rs757081) in the rest of the cohort using TaqMan probe. Five variants, including c.1012C>G (Q338E) were found. Genotyping for c.1012C>G found that the GG genotype was significantly less frequent in the obese group; odds ratio for obese subjects carrying the CC and CG genotypes was 2.29 (95% CI 1.17-4.49) in the dominant model, CC genotype 2.86 (95% CI 1.41-5.81) in the additive model, and C allele 1.57 (95% CI 1.17-2.1). The findings were replicated in an independent cohort of 372 obese and 390 normal weight Chinese children, where the odds ratio of obese subjects with CC and CG genotypes was 1.69 (95% CI 1.12-2.55). Within the Da Qing cohort, subjects with the GG genotype had significantly lower BMI and percentage ideal weight for height (WFH) at 5 and 8years of age. Subjects with lower birth weights also had more pronounced difference in WFH and BMI at 5 and 10years of age between GG subjects versus CC/CG subjects. We postulate that GG genotype is protective against excessive weight gain, and factors which predispose to excessive weight gain such as higher birth weights may ameliorate the effect.