The Gene-Gene Interaction of INSIG-SCAP-SREBP Pathway on the Risk of Obesity in Chinese Children

الملخص EN

Background.

Childhood obesity has become a global public health problem in recent years.

This study aimed to explore the association of genetic variants in INSIG-SCAP-SREBP pathway with obesity in Chinese children.

Methods.

A case-control study was conducted, including 705 obese cases and 1,325 nonobese controls.

We genotyped 15 single nucleotide polymorphisms (SNPs) of five genes in INSIG-SCAP-SREBP pathway, including insulin induced gene 1 (INSIG1), insulin induced gene 2 (INSIG2), SREBP cleavage-activating protein gene (SCAP), sterol regulatory element binding protein gene 1 (SREBP1), and sterol regulatory element binding protein gene 2 (SREBP2).

We used generalized multifactor dimensionality reduction (GMDR) and logistic regression to investigate gene-gene interactions.

Results.

Single polymorphism analyses showed that SCAP rs12487736 and rs12490383 were nominally associated with obesity.

We identified a 3-locus interaction on obesity in GMDR analyses (P=0.001), involving 3 genetic variants of INSIG2, SCAP, and SREBP2.

The individuals in high-risk group of the 3-locus combinations had a 79.9% increased risk of obesity compared with those in low-risk group (OR=1.799, 95% CI: 1.475–2.193, P=6.61×10-9).

Conclusion.

We identified interaction of three genes in INSIG-SCAP-SREBP pathway on risk of obesity, revealing that these genes affect obesity more likely through a complex interaction pattern than single gene effect.