Kunnas Tarja, Määttä Kirsi, Nikkari Seppo T
Department of Medical Biochemistry, University of Tampere Medical School and Fimlab laboratories, Tampere, Finland.
Int J Med Sci. 2016 Apr 10;13(5):325-9. doi: 10.7150/ijms.14849. eCollection 2016.
Oxidative stress is involved in the pathophysiology of many cardiovascular disorders, such as hypertension and atherosclerosis. NRF2 is the primary transcriptional regulator of several antioxidant genes, including that of sulfiredoxin (SRXN1). The association of genotypes of NRF2 and SRXN1 with cardiovascular conditions was studied in a Finnish cohort of 336 subjects with diagnosed hypertension and 480 normotensive controls from the Tampere adult population cardiovascular risk study (TAMRISK). Samples were genotyped for four SNPs (rs1962142, rs2706110, rs6721961 and rs6706649) in the NRF2 gene region and four SNPs (rs6053666, rs6116929, rs2008022, rs6085283) in the SRXN1 gene region using Competitive Allele Specific PCR (KASP) technique. Cardiovascular diseases were followed up from 2005 to 2014 using the Finnish National Hospital Discharge Registry (HILMO). Four out of eight studied polymorphisms: rs6721961, rs1962142, rs2706110 of NRF2, and rs6053666 of SRXN1 were associated with cerebrovascular disease. NRF2 polymorphism rs6721961 showed association with hypertension. NRF2 and SRXN1 polymorphisms, previously thought to be associated with human disease, appear to be associated particularly with cerebrovascular disease.
氧化应激参与许多心血管疾病的病理生理过程，如高血压和动脉粥样硬化。NRF2是几种抗氧化基因的主要转录调节因子，包括硫氧还蛋白（SRXN1）的转录调节因子。在来自坦佩雷成年人群心血管风险研究（TAMRISK）的336名已诊断高血压患者和480名血压正常对照组成的芬兰队列中，研究了NRF2和SRXN1的基因型与心血管疾病的关联。使用竞争性等位基因特异性PCR（KASP）技术对NRF2基因区域的四个单核苷酸多态性（SNP，rs1962142、rs2706110、rs6721961和rs6706649）以及SRXN1基因区域的四个SNP（rs6053666、rs6116929、rs2008022、rs6085283）进行基因分型。利用芬兰国家医院出院登记系统（HILMO）对2005年至2014年的心血管疾病进行随访。所研究的八个多态性中的四个：NRF2的rs6721961、rs1962142、rs2706110以及SRXN1的rs6053666与脑血管疾病相关。NRF2多态性rs6721961与高血压相关。以前认为与人类疾病相关的NRF2和SRXN1多态性，似乎尤其与脑血管疾病相关。
