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.
ABSTRACT
Objective To explore the interaction between polymorphisms of rs17222919 which located in the 5-1ipoxygenase-activating protein(ALOX5AP) gene promoter and environmental risk factors in ischemic stroke(IS).Methods We conducted a case-control study involving a total of 622 cases and 631 unrelated healthy controls which were selected from Henan Han populations,and the environment risk factors were recorded.Genotyping aimed at detecting both genetic and environmental factors in relation to IS was performed by TaqMan-polymerase chain reaction technology while interaction indexes (Υ) were calculated to determine interactions and their role models.Results The rs17222919 TG (189/622,30.4％),GG (18/622,2.9％)genotype frequencies and G (225/1244,18.1％)allele frequencies in IS subjects were significantly lower than those in controls (221/631,35.0％ ; 31/631,4.9％ ; 283/1262,22.4％ ; x2 =4.117,P =0.042 ; x2 =4.457,P =0.035 ; x2 =7.294,P =0.007).Negative interactions between TG + GG genotype and hypertension,diabetes or cigarette smoking in the occurrence of IS (Υ =0.943,0.922,0.830) were observed,whose role models were all super-multiplicative models.Conclusions According to our study,ischemic stroke is the result of the interaction of genetic and environmental factors and G allele of rs17222919 may have weakened the role of environmental factors for hypertension,diabetes and cigarette smoking in IS incidence.
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Objective To explore associations between SG13S114A/T and SG13S32A/C polymorphisms of ALOX5AP gene and the genetic susceptibility of ischemic cerebrovascular diseases (ICVD) in Henan Han population.Methods Two hundred and forty-six ICVD patients and 245 healthy controls were recruited from Han population in Henan province. Polymorphisms of SG13S114A/T and SG13S32A/C in ALOX5AP gene were genotyped in these samples by SnaPshot minisequencing method.Each genotype frequency and allele frequency were statistically analyzed and compared between ICVD group and control group using SPSS16.0 software.Haplotype and linkage disequilibrium were analyzed by SHEsis software.Results The SG13S114 AA genotype frequency ( 18.7％ ) and A allele frequency (41.3％) in ICVD group were significantly higher than those in control group (9.0％ and 32.7％,respectively; P =0.002 and P =0.005 ).It was also found that in male ICVD group and in younger ICVD group ( ＜50 years old),the SG13S114 AA genotype frequencies (22.1％ and 22.0％,respectively) and A allele frequencies (42.1％ and 42.7％,respectively) were significantly higher than those in male control group and younger control group (SG13S114 AA genotype:9.0％ and 8.9％ ; P =0.010 and P =0.006,respectively) ;A allele frequencies,34.0％ and 32.0％ ; P =0.048 and P =0.020,respectively.Finally,the prevalence of A-A haplotype in ICVD group was significantly higher than that in control group(30.4％ vs 23.5％,OR =1.419,95％ CI 1.068-1.885,P =0.015).T-C haplotype frequency of ICVD group was significantly lower than that in control group (22.0％ vs 28.8％,OR =0.698,95％ CI 0.523-0.932,P =0.014 ).Conclusions The A allele in SG13S114 loci of ALOX5AP may be a genetic risk factor for ICVD in Han population in Henan province.The association is predominant in ICVD patients of male and younger than 50 years old.Maybe A-A haplotype increases the risk of ICVD and T-C haplotype and has a protective effect against ICVD in Henan Han population.
ABSTRACT
Cerebral infarction is a polygenic disease caused by genetic factors and environmental factors.The first discovery in the Icelanders is that the ALOX5AP and PDE4D gene polymorphism may be associated with cerebral infarction.So far,many conclusions of foreign studies are still controversial.This article will summarize the research status and the progress of these two genes.