Kunnas Tarja, Määttä Kirsi, Nikkari Seppo T
Department of Medical Biochemistry, Faculty of Medicine and Health Technology Tampere University and Fimlab Laboratories, Tampere, Finland.
Medicine (Baltimore). 2021 Oct 22;100(42):e27566. doi: 10.1097/MD.0000000000027566.
We have previously shown an association of STK39 (serine threonine kinase) rs6749447 (T > G) with hypertension in the Tampere adult population cardiovascular risk study in 50-year-old subjects. These 1196 subjects were followed up to the age of 65 years to determine whether rs6749447 is also associated with coronary artery disease (CAD), transient ischemic attack (TIA), or early cardiovascular death.DNA samples were collected by buccal swabs and genotypes were determined by PCR. Hypertension, TIA, and CAD were determined by questionnaire and the National Hospital Discharge Registry. Outcomes for death were collected from the National Statistics Centre. Linkage disequilibrium analysis and gene expression correlations for rs6749447 were done in silico.After following the subjects up to the age of 60 years the rs6749447 G-allele still associated with hypertension (P = .009). The variation did not associate with CAD (P = .959). The risk for TIA was 5.2-fold among G-allele carriers compared to TT genotype even after adjusting for body mass index (P = .036, 95% CI 1.11-24.59). After follow-up of the subjects to the age of 65 years, adjusting for body mass index, the G-allele was associated with 3.2-fold risk of premature cardiovascular death (P = .049, 95% CI 1.00-10.01).In conclusion, the STK39 genetic variant rs6749447 was significantly associated with TIA and premature cardiovascular death in a Finnish cohort. The in silico results of linkage disequilibrium and gene expression analyses also showed associations that were distinct from the retention of salt effect on kidneys proposed earlier for this intronic variation.
在坦佩雷成人人群心血管风险研究中,我们之前已表明,STK39(丝氨酸苏氨酸激酶)基因的rs6749447(T > G)与50岁受试者的高血压有关。对这1196名受试者随访至65岁,以确定rs6749447是否也与冠状动脉疾病(CAD)、短暂性脑缺血发作(TIA)或早期心血管死亡相关。通过口腔拭子收集DNA样本,并通过聚合酶链反应确定基因型。通过问卷和国家医院出院登记处确定高血压、TIA和CAD。从国家统计中心收集死亡结果。对rs6749447进行连锁不平衡分析和基因表达相关性的计算机模拟分析。在对受试者随访至60岁时,rs6749447的G等位基因仍与高血压相关(P = 0.009)。该变异与CAD无关(P = 0.959)。即使在调整体重指数后,G等位基因携带者发生TIA的风险是TT基因型携带者的5.2倍(P = 0.036,95%可信区间1.11 - 24.59)。在对受试者随访至65岁时,调整体重指数后,G等位基因与心血管过早死亡风险增加3.2倍相关(P = 0.049,95%可信区间1.00 - 10.01)。总之,在芬兰队列中,STK39基因变异rs6749447与TIA和心血管过早死亡显著相关。连锁不平衡和基因表达分析的计算机模拟结果也显示出一些关联,这些关联与之前提出的该内含子变异对肾脏的保盐作用不同。