PTEN Gene Polymorphism And Haplotypes With Atherosclerotic Cerebral Infarction

BackgroundCerebral infarction (CI) is a global public health problem with a high incidence of morbidity, disability, mortality and recurrence rate, which does serious harm to human health. Ischemic stroke is a complex multi-gene disease caused by a variety of genetic and environmental factors, among which atherosclerosis (AS) is the leading etiology. Evidences from twins, families and different races studies have shown that the genetic factors have played an important role in the development of CI, as well as environmental factors. However, few of the publicly accepted responsible genes have been picked out yet, and most of the positive findings could not be reduplicated, while some results even contradicted with each other, owing to the high phenotypic heterogeneity and genetic heterogeneity.Phosphatase and tensin homology deleted on chromosome ten (PTEN) is a tumor suppressor gene which has dual phosphatase activity and can regulate the cell cycle and induce apoptosis of tumor cells and inhibit the growth, invasion and metastasis of tumor cells. Recent studies have shown that PTEN has anti-inflammatory activity, and increased PTEN can reduce the expression of LPS-induced vascular cell adhesion molecules (VCAM-1), which can effectively prevent the development of atherosclerosis and reduce the incidence of cardiovascular diseases. To date, studies on the relationship between the polymorphisms of PTEN and atherosclerotic cerebral infarction (ACI) have not been reported at home or abroad.ObjectiveTo explore the relationship between the SNP and Haplotype of five sites of PTEN genes (rs2299939,rs17431184,rs555895,rsl2357281and rs2673836) and atherosclerosis cerebral infarction(ACI) among Chinese Han Nation in Hunan.Methods300 ACI patients and 204 healthy controls were selected for the present study. The five SNPs (rs2299939, rs17431184, rs555895, rsl2357281 and rs2673836) were detected using PCR and MALDI-TOF-MS. Linkage disequilibrium and haplotype analysis were conducted among the SNPs which turned out to be have a positive association with ACI(rs2299939,rs17431184 and rs555895). Then we studied the relationship between different genotypes and haplotypes and the risk of ACI.Results1. The SNPs of rs2299939 A/C,rs17431184 C/T and rs555895 G/T existed among Chinese Han Nation in Hunan. And the SNPs of rs12357281C/G and rs2673836A/G were not found.2. The AA/AC/CC genotype frequencies of rs2299939 in ACI group and control group were 0.033/0.277/0.690 and 0.054/0.593/0.353 respectively. The C/T allele frequencies in ACI group and control group were 0.173/0.827 and 0.350/0.650 respectively. There were significant differences in genotype distribution and allele frequencies between the two groups(P<0.05). The CC genotype and the C allele frequency were both higher in ACI group than in control group(P<0.05).3. The CC/CT/TT genotype frequencies of rs 17431184 in ACI group and control group were 0.033/0.370/0.597 and 0.044/0.382/0.574 respectively. The C/T allele frequencies in CI group and control group were 0.218/0.782 and 0.235/0.765 respectively. There were no significant differences in genotype distribution and allele frequencies (P>0.05) between the two groups.4. The GG/GT/TT genotype frequencies of rs555895 in ACI group and control group were 0.286/0.457/0.257 and 0.152/0.559/0.289 respectively. The C/T allele frequencies in ACI group and control group were 0.493/0.507 and 0.431/0.569 respectively. There were no significant differences in genotype distribution and allele frequencies (P>0.05) between the two groups.5. There were linkage disequilibrium between the PTEN gene SNPs of rs2299939,rs17431184 and rs555895. And the linkage between rs2299939 and rs17431184 was more close than the two others(D'=0.808, r2=0.588).6. The results showed that the haplotype frequency of rs2299939 C-rs17431184 T- rs555895 T was significantly higher in ACI group than in control group(P<0.01).7. The logistic regression result shows that the influence factors of ACI include sex, BMI, smoking, coronary heart disease, hypertension, fasting blood glucose, DBP and the CC genotype of SNP rs2299939.Conclusions1. The SNPs of rs2299939 A→C may be the risk factor of ACI among Chinese Han Nation in Hunan.2. The haplotype C-T-T comprised of rs2299939C/rs17431184T/rs 555895T may be the risk factor of ACI among Chinese Han Nation in Hunan.3. It is probable that the Polymorphism of PTEN rs555895G→T and rs17431184C→T are independent on the occurrence of ACI. 4. The SNPs of rs 12357281 C/G and rs2673836A/G may not exist among Chinese Han Nation in Hunan.