| Background and purpose:Stroke, characters of high disease incidence, high death rate, high disability rate, and high recurrence rate, has become an important health problem worldwide. It is a frequent cerebrovascular disease in China, and it is still a leading cause of mortality and morbidity in Chinese. The pathogenesis of stoke remains unclear, but it has been established that the underlying pathogenesis is likely to be mediated by both genetic and environmental factors. Human telomeres, consisting of TTAGGG repetitive sequences and some binding proteins, located at the ends of chromosomes. In normal cells, telomeres would shorten gradually with cell replication. Previous study indicated that some genes would influence the telomere length, including ACYP2, TERT, TERC, OBFC1, NAF1, RTEL1, ZNF208 etc.. However, whether these genes were associated with stroke is still unknown. Therefore, we investigated whether these gene polymorphisms were associated with stroke risk and the impact of telomere length on stroke risk.Methods:We recruited 300 stroke and 300 control subjects from the First Affiliated Hospital of Xi'an Jiaotong University to analysis the association between the 50 selected single nucleotide polymorphisms and the stroke susceptibility via the case-control method. The blood genomic DNAs were extracted with commercial kits. Genotyping was performed by using the sequenom MassARRAY RS1000 platform. We used the exact test to confirm whether the tSNPs of the control group meet Hardy-Weinberg equilibrium (HWE). We used the x2 analysis and SNPStats software to calculate the odds ratios (OR) and the 95% confidence intervals (95%CI) of risk allele to evaluate the power of risk allele. We adopted the Haploview software (version 4.2) to calculate the linkage degree as well as construct haplotypes in order to evaluate haplotype effect. Telomere length was measured by quantitave real-time PCR with genomic DNA of 300 cases and 300 controls. Unconditional logistic regressions were used to calculate adjusted odds ratios (OR) with 95% confidence intervals (95%CI) as the indicator of association between telomere length and stroke risk.Results:Based on ?2 test, rs2853677 (TERT), rs10936599 (MYNN), rs2188971, rs8103163, rs7248488 (ZNF208), and rs11125529, rs12615793, rs843711, rs11896604, rs843706, rs17045754 (ACYP2) were associated with the risk of stroke.The genetic model analysis indicated that:under the Log-additive model, ACYP2 rs11125529, rs12615793, rs843711, rs11896604, rs843706 and rs17045754 loci polymorphisms were significantly associated with increased risk of stroke. Under the dominant model, genotype "C/A-C/C" of rs10439478 in ACYP2 increased the risk of stroke. TERT rs2853677 associated with increased stroke risk by 1.91-fold under the Co-dominant model. TERT rs2242652 influence the risk of stroke under Overdominant model. Rs1056654 in MPHOSPH6 may reduce the risk of stroke in the recessive model. ZNF208 rs2188971, rs8103163 and rs7248488 increased stroke risk in the Log-additive model.Using Haploview software we found SNPs of ACYP2, MPHOSPH6 and ZNF208 are strongly linked, and the "TTCTAATG" haplotype may significantly increase the risk of stroke. Four SNPs (rs2188972, rs2188971, rs8103163, rs7248488) in ZNF208 were in the same linkage disequilibrium block. Within this linkage disequilibrium block, haplotype "CTCAAC" showed an increased risk of stroke.On the basic of measuring telomere length of 300 stoke cases and 300 healthy individuals, we observed that telomere length of stroke patients s are obviously shorter than normal controls.Conclusions:Our results provide independent evidence that the ACYP2, TERT, MPHOSPH6 and ZNF208 genes may be associated with stroke risk in the Chinese Han population. However, our results need further research. Additionally, we also found that telomere length is closely associated with the risk of stroke. |
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