CAJ | 학술논문

目的对中国浙江南部地区人群花生四烯酸代谢脂氧合酶通路5-脂氧合酶激活蛋白基因(ALOX5AP基因)4个单核苷酸多态性(SNPs)和细胞色素P450酶(CYP450)通路4个SNPs的多态性进行研究,探讨基因多态性、基因-基因间联合交互作用与脑梗死的患病风险的相关性.方法采用病例对照设计,测定了292例脑梗死患者和259例对照者8个基因位点,包括ALOX5AP基因的4个位点:SG13S32(rs9551963)、SG13S42(rs4769060)、SG13 S89(rs4769874)、SG13Sl14(rs10507391),及EPHX2基因G860A(rs751141)、CYP2C9*2基因A1075C (rs1057910)、CYP2C9*3基因C430T(rs1799853)和CYP3A5基因A6986G(rs776746)位点SNPs.应用广义多因子降维法(GMDR)软件检测基因与基因之间的交互作用.结果脑梗死组和对照组中8个候选基因位点的基因型分布在脑梗死组和对照组间比较差异无统计学意义.GMDR方法显示最优模型为SG13Sl14和A6986G两基因联合作用模型,其样本检验准确度56.32％,交叉检验一致性为10/10,符号检验P=0.011.调整年龄、高血压、糖尿病因素后SG13S114和A6986G交互变量与脑梗死患病风险正相关(OR=1.804,95％CI1.180～2.759,P=0.006).结论 SG13Sl14和A6986G基因联合交互作用显著增加脑梗死患病风险.对基因与基因间的交互作用分析,有助于更深入地研究复杂疾病的基因型和表型间的关系.
목적 대중국절강남부지구인군화생사희산대사지양합매통로5-지양합매격활단백기인(ALOX5AP기인)4개단핵감산다태성(SNPs)화세포색소P450매(CYP450)통로4개SNPs적다태성진행연구,탐토기인다태성、기인-기인간연합교호작용여뇌경사적환병풍험적상관성.방법 채용병례대조설계,측정료292례뇌경사환자화259례대조자8개기인위점,포괄ALOX5AP기인적4개위점:SG13S32(rs9551963)、SG13S42(rs4769060)、SG13 S89(rs4769874)、SG13Sl14(rs10507391),급EPHX2기인G860A(rs751141)、CYP2C9*2기인A1075C (rs1057910)、CYP2C9*3기인C430T(rs1799853)화CYP3A5기인A6986G(rs776746)위점SNPs.응용엄의다인자강유법(GMDR)연건검측기인여기인지간적교호작용.결과 뇌경사조화대조조중8개후선기인위점적기인형분포재뇌경사조화대조조간비교차이무통계학의의.GMDR방법현시최우모형위SG13Sl14화A6986G량기인연합작용모형,기양본검험준학도56.32％,교차검험일치성위10/10,부호검험P=0.011.조정년령、고혈압、당뇨병인소후SG13S114화A6986G교호변량여뇌경사환병풍험정상관(OR=1.804,95％CI1.180～2.759,P=0.006).결론 SG13Sl14화A6986G기인연합교호작용현저증가뇌경사환병풍험.대기인여기인간적교호작용분석,유조우경심입지연구복잡질병적기인형화표형간적관계.
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.