Interactions among genetic variants from SREBP2 activating-related pathway on risk of coronary heart disease in Chinese Han population

Xiaoli Liu, Yun Li, Xiangfeng Lu, Laiyuan Wang, Qi Zhao, Wei Yang, Jianfeng Huang, Jie Cao, Hongfan Li, Dongfeng Gu

Research output: Contribution to journalArticle

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Abstract

Sterol regulatory element binding proteins (SREBPs), as a family of membrane-bound transcription factors, control the metabolism of cholesterol and fatty acids. We conducted a case-control study to investigate whether the common variants of genes from the SREBP2 activating-related pathway, involving SREBP2, SCAP, INSIG1 and INSIG2 genes, were associated with coronary heart disease (CHD) of Chinese Han population individually or interactively. Three, four and two single nucleotide polymorphisms (SNPs) from the INSIG1, INSIG2 and SCAP genes were chosen as haplotype-tagging SNPs (htSNPs), respectively, and one nonsynonymous coding SNP was selected from SREBP2. All of the SNPs were genotyped in 853 CHD cases and 948 unrelated control subjects. The interactions among SNPs of the four genes were evaluated with multifactor-dimensionality reduction (MDR) and logistic regression models (LRM). The results from MDR indicated that there existed the SNP-SNP interactive effect of INSIG1 gene on CHD (best prediction accuracy = 56.09%, p = 0.002 on 1000 permutations). The results from LRM also identified the 2-locus interaction model (adjusted p ≤ 0.001 for interaction) as well as the 3-locus gene-gene interaction (adjusted p = 0.026 for interaction). Single polymorphism analysis showed that the rs4822063 of SREBP2 was associated with LDL-C in the controls. The genotype CC carriers had higher LDL-C than the major allele G carriers (3.44 ± 0.90 mmol/L versus 3.17 ± 0.84 mmol/L, adjusted p = 0.038). Our results suggested that the INSIG1 gene was associated with CHD; there might be potential interactive effect on CHD among genes from SREBP2 activating-related pathway; and the SREBP2 gene might be associated with plasma lipid level.

Original languageEnglish (US)
Pages (from-to)421-426
Number of pages6
JournalAtherosclerosis
Volume208
Issue number2
DOIs
StatePublished - Feb 1 2010
Externally publishedYes

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Coronary Disease
Single Nucleotide Polymorphism
Population
Genes
Multifactor Dimensionality Reduction
Logistic Models
Sterol Regulatory Element Binding Proteins
Haplotypes
Case-Control Studies
Transcription Factors
Fatty Acids
Alleles
Cholesterol
Genotype
Lipids
Membranes

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

Interactions among genetic variants from SREBP2 activating-related pathway on risk of coronary heart disease in Chinese Han population. / Liu, Xiaoli; Li, Yun; Lu, Xiangfeng; Wang, Laiyuan; Zhao, Qi; Yang, Wei; Huang, Jianfeng; Cao, Jie; Li, Hongfan; Gu, Dongfeng.

In: Atherosclerosis, Vol. 208, No. 2, 01.02.2010, p. 421-426.

Research output: Contribution to journalArticle

Liu, Xiaoli ; Li, Yun ; Lu, Xiangfeng ; Wang, Laiyuan ; Zhao, Qi ; Yang, Wei ; Huang, Jianfeng ; Cao, Jie ; Li, Hongfan ; Gu, Dongfeng. / Interactions among genetic variants from SREBP2 activating-related pathway on risk of coronary heart disease in Chinese Han population. In: Atherosclerosis. 2010 ; Vol. 208, No. 2. pp. 421-426.
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AU - Zhao, Qi

AU - Yang, Wei

AU - Huang, Jianfeng

AU - Cao, Jie

AU - Li, Hongfan

AU - Gu, Dongfeng

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