| BackgroundCognitive impairment is a common complication in stroke patients and has enormous results for patient's life, their families, and society. Many risk factors(such as education, age ,hypertension and cholesterol) can effect cognitive impairment with stroke. Moreover, brain injury caused by the same or similar risk factors can induce different degree cognitive impairment in clinic. Several studies have shown that estrogen therapy improves cognitive function in elderly women, and the protection of estrogen is mediated by the estrogen receptor(ER). The gene for the ERαhas several single nucleotide polymorphisms (SNPs), the PvuΙΙ, XbaΙ,and B-variants, that may be associated with receptor expression and function. Recent study showed estrogen receptorα(ERα) gene polymorphism is associated with the risk of stroke and cognitive impairment in normal elderly people. Importantly,the association of genotype with risk of stroke was independent of established cardiovascular risk factors, including diabetes, and was essentialy unchanged after exclusion of stroke cases with coronary heart disease. Therefore,genetic factors may be related to cognitive impairment with stroke except for the above risk factors. However, the relationship between ERαgene polymorphism and cognitive impairmen in the patients with sroke is not clear.In our research, we firstly compared the distrubution of ERαgene polymorphism in both normal and stroke patients, Secondly, the relationship of ERαgene polymorphism and cognitive impairment in stroke patients was analyzed. Finally, the role of ERαgene polymorphism in the development of cognitive impairment in patients with stroke was discussed to provide the experimental and theoretical evidence for the early intervention of vascular cognitive impairment in clinic. Subjects and MethodsStudy population: The study included 568 healthy medical examination cases of Han people, with mean age 63.48±11.16 years old (358 male and 162 female). Stroke inpatients, with mean age 65.45±11.27 years old (298 male and 182 female), were also included in the research. The stroke was defined according to the"Diagnositic Main Points of Cerebrovascular Disease"passed by the 4th national cerebrovascular disease academic seminar conducted by Chinese Medical Association in 1995.Methods: The alleles of the ERαgene polymorphism were detected using polymerase chain reaction and subsequent cleavage by XbaI and PVuII restriction endonuclease. The distribution frequencies of genotypes and alleles were calculated. Cognitive function of stroke population was evaluated by MMSE and SECF methods. According to the score of MMSE and SECF, the stroke patients were divided into normal congnitive funtion and cognitive impairment groups.Results1. In Chongqing district, the Pp, xx and ppxx genotypes of ERαgene had more population than other genotypes. No ppXX genotype of female was detected. No significance of the distributions of ERαgenotypes and alleles was observed between male and female subjects.2. Pp, xx and ppxx genotypes of ERαgene in stroke patients had more population than other genotypes. Both female and male stroke patients had a higher XX genotype and X allele distribution frequency than that of normal population.3. MMSE detection showed that the ratio of cognitive impairment patients was 24.8%. Both female and male stroke patients with cognitive impairment had a higher XX genotype and X allele distribution frequency than that of normal population. Female stroke patients with cognitive impairment had a higher Pp genotype frequency than that of normal population.4. SECF detection showed that the ratio of cognitive impairment patients was 50.2%. Female stroke patients with cognitive impairment had a lower X allele distribution frequency than patients with normal cognitive function. No XX genotype in female with abnormal SECF score was dectected. The distribution frequencies of XX genotype and X allele of male with abnormal SECF score were higher than those of normal population. 5. Age, educational level, the degree of neurologic impairment, TC and LDL were all related with cognitive impairement. The relative risk of cognitive impairement of Pp genotype was 3.81 times than that of PP genotype.Conclusion1. In Chongqing district, the Pp, xx and ppxx genotypes of ERαgene had more population than other genotypes.2. Pp, xx and ppxx genotypes of ERαgene in stroke patients had more population than other genotypes. XX genotype and X allele were the predisposing genes of stroke patients.3. Age, educational level, the degree of neurologic impairment, TC and LDL were the risk factors of cognitive impairement in stroke patients.4. XX genotype, X allele and Pp genotype were the predisposing genes of cognitive impairement in stroke patients. Female patients with X allele and Pp genotype had more dangerous suffering cognitive impairement. Pp genotype was independent of stroke and was the only predisposing gene of female stroke patients.
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