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Biomed Res Int. 2014;2014:538564. doi: 10.1155/2014/538564. Epub 2014 Jun 17.

The gene-gene interaction of INSIG-SCAP-SREBP pathway on the risk of obesity in Chinese children.

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1
School of Public Health, Institute of Child and Adolescent Health, Peking University, No. 38 Xueyuan Road, Haidian District, Beijing 100191, China.

Abstract

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.

PMID:
25028659
PMCID:
PMC4083216
DOI:
10.1155/2014/538564
[Indexed for MEDLINE]
Free PMC Article
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