The Study On The Relationship Between SNPs In IMD/ADM2、RAMPs Genes And Ischemic Stroke

Intermedin/Adrenomedullin2(IMD/ADM2) and receptor activity modifying proteins,RAMPs) are reported to be protective factors for hypertension,atherosclerosis and endothelial injury, however, the relationship between their single nucleotide polymorphisms and stroke is unclear.Objective:The aim of the study is to investigate the relationship between the IMD/ADM2polymorphisms and ischemic stroke in a haplotype-base analysis.Methods:The patients, diagnosised in accordance with the1982International Nervous System Related Diseases Association and clasified in accordance with the TOAST classification system, were recruited in the study. Those cases, who got treatments in the Neurologic Department and Geriatric Department from the April2012to February2013,had the types of the large-artery atherosclerosis ischemic stroke and small-artery occlusion. Controls were the healthy ones getting physical examination in our hospital. The automatic biochemical analysing systems were used to detect the blood routine and biochemical indicators. Phenol-chloroform was used to extract DNA from the whole blood. Genetyping was performed by using the PCR-RFLP assay. Results:1. Basic characteristics and traditional risk factors of the subjectsThere was154patients in the cases and114controls.The mean age was63.01±11.14years old for the cases and60.57±12.68years for the control;74.68%cases and84.21%controls were male,25.32%cases and15.79%controls were female, there was no difference in the distribution of age and sex between the cases and controls(p=0.097、0.0579). The traditional risk factors, including smoking, hypertension and diabete had high proportion in the cases than that in controls,while BMI, triglycerides, total cholesterol, low-density lipoprotein don’t(p=0.085、0.511、0.064、0.262). Drinking、uric acid had a difference in the two groups, however, they were not the he risk factors in this study revealed by the multivariate logistic regression analysis. Simultaneously, the distribution of platelet count and mean platelet volume was significant different(p=0.005、0.002).2. Genotype and allele distribution in the two groups and the multivariate logistic regression analysisThere was a deviation from the Hardy-Weinberg equilibrium(HWE) in the following controls tested:rs2236031, rs876278, rs3754704. For rs2074654, the genotype and allele distribution had an obvious difference between the two groups (p=0.000,0.000); correlation analysis revealed that there was a low correlation between rs2074654and ischemic stroke, the correlation coefficientis was0.308; compared to wide type TT, the heterozygous type CT genotype and CC+CT genetype had an increased risk of stroke (OR=4.757,6.749,95%CI=(2.264-9.996),(3.270-13.928)); when fully adjusted by smoking, hypertension, diabete, nertrophil ratio, platelet count and mean platelet volume, rs2074654CT genetype played a high risk of ischemic stroke((OR=5.813,95%CI=1.511-11.364)); compared to TT genetype,the CT+CC genetype also had a high risk of ischemic stroke (OR=10.927(2.991-39.927)); the risk disappears in the comparion of TT+CT genetype to CC genetype.Conclusion:This study suggested that rs2074654polymorphism in RAMP3gene may contribute to ischemic stroke. The C allele and CT genotype are likely to be biomarkers of ischemic stroke susceptible population. Larger sample studies and functional studies are needed to conform this finding. And the relationship between IMD/ADM2rs2236031, rs876278, RAMP1rs3754704polymorphism and stroke also need further studies.