Association of INSIG2 polymorphism with overweight and LDL in children

Abstract

Background: Dyslipidemia and overweight are common issues in children. Identifying genetic markers of risk could lead to targeted interventions. A polymorphism of SNP rs7566605 near insulin-induced gene 2 (INSIG2) has been identified as a strong candidate gene for obesity, through its feedback control of lipid synthesis.

Objective: To identify polymorphisms in INSIG2 which are associated with overweight (BMI ≥ 85% for age) and dyslipidemia in children.

Hypothesis: The C allele of rs7566605 would be significantly associated with BMI and LDL.

Design/methods: We genotyped 15 SNPs in/near INSIG2 in 1,058 healthy children (53% non-Hispanic white (NHW), 37% overweight) participating in a school based study. Genotype was compared with BMI and lipid markers, adjusting for age, gender, and puberty.

Results: We found a significant association between the SNP rs12464355 and LDL in NHW children, p < 0.001. The G allele is protective (lower LDL). A different SNP was associated with overweight in NHW: rs17047757. SNP rs7566605 was not associated with overweight or lipid levels.

Conclusions: We identified novel genetic associations between INSIG2 and both overweight and LDL in NHW children. Polymorphisms in INSIG2 may be important in the development of obesity through its effects on lipid regulation.

Figure 1. Linkage disequilibrium as measured by r² across INSIG2 in Non-Hispanic Whites.

Figure 2. Linkage disequilibrium as measured by r² across INSIG2 in African-Americans.

Figure 3. G allele of SNP rs12464355 in the INSIG2 gene is associated with lower LDL levels, p< 0.001 in Non-Hispanic Whites.

Least Square Adjusted Mean of LDL (mg/dl) is shown. Predicted values are given from a multiple regression analysis, adjusting for age, gender, and pubertal stage. LDL levels were ln transformed and back converted.