Interactions between 5-1ipoxygenase-activating protein and cytochrome P450 3A5 gene variants significantly increase the risk of cerebral infarction / 中华神经科杂志

ABSTRACT

Objective To investigate 4 variants single nucleotide polymorphisms (SNPs) of 5-lipoxygenase-activating protein(ALOX5AP) in lipoxygenase pathway and in cytochrome P450 pathway as susceptibility genes for stroke in a southeastern Chinese population,and evaluate the associations between susceptibility genes and cerebral infarction,to find whether gene-gene interactions increase the risk of cerebral infarction.Methods By case-control study,two hundred and ninety-two patients with cerebral infarction and 259 healthy control subjects were included.Eight variants in 5 candidate genes were examined for stroke risk,including the SG13S32 (rs9551963),SG13S42 (rs4769060),SG13S89 (rs4769874),and SG13Sl14 (rs10507391) variants of the ALOX5AP gene,the G860A (rs751141) variant of the soluble epoxide hydrolase (EPHX2) gene,the A1075C (rs1057910) variant of the CYP2C9 *2 gene,the C430T (rs1799853) variant of the CYP2C9* 3 gene,and the A6986G (rs776746) variant of the CYP3A5 gene.Gene-gene interactions were explored using generalized multifactor dimensionality reduction (GMDR)methods.Results There were no statistically significant differences in the frequencies of the genotypes of the 8 candidate genes.The GMDR analysis showed a significant gene-gene interaction between SG13S114 and A6986G,with scores of 10 for cross-validation consistency and 9 for the sign test (P =0.011).These genegene interactions predicted a significantly higher risk of cerebral infarction (adjusted for age,hypertension,and diabetes mellitus;OR =1.804,95％ CI 1.180-2.759,P =0.006).Conclusions A two-loci gene interaction confers significantly higher risk for cerebral infarction.The combinational analysis used in this study may be helpful in the elucidation of genetic risk factors for common and complex diseases.