Abstract
Hypertension (HT) is a major risk factor for cardiovascular diseases. Krüppel-like factors (KLFs) are important transcription factors in eukaryotes. Studies have reported that KLF4 and KLF5 are correlated with several cardiovascular diseases, but population-based studies on associations between HT and KLF4 or KLF5 have rarely been reported. Therefore, the current study investigated the associations of genetic variants and mRNA expression levels of KLF4 and KLF5 with HT, as well as the effects of antihypertensive drugs on the expression levels of these genes. The associations of one single-nucleotide polymorphism (SNP) in KLF4 and three SNPs in KLF5 with HT were analyzed using a combination of case-control and cohort studies. The study populations were selected from a community-based cohort in four regions of Jiangsu province. The risks of HT were estimated through logistic and Cox regression analyses. In addition, mRNA expression levels of KLF4 and KLF5 were detected in 246 controls and 385 HT cases selected from the aforementioned cohort. Among the HT cases, 263 were not taking antihypertensive drugs [AHD(-)] and 122 were taking antihypertensive drugs [AHD(+)]. In the case-control study, SNP rs9573096 (C>T) in KLF5 was significantly associated with an increased risk of HT in the additive model (adjusted odds ratio [OR], 1.106; 95% confidence interval [CI], 1.009 to 1.212). In the cohort study of the normotensive population, rs9573096 in KLF5 was also significantly associated with an increased risk of HT in the additive model (adjusted hazards ratio [HR], 1.199; 95% CI, 1.070 to 1.344). KLF4 and KLF5 mRNA expression levels were significantly higher in the AHD(-) group than in the control group ( P < 0.05), but lower in the AHD(+) group than in the AHD(-) group ( P < 0.05). The current study demonstrated the associations of KLF4 and KLF5 genetic variants with hypertension, as well as the association of the indicative variations in mRNA expression levels of KLF4 and KLF5 with the risk of hypertension and antihypertensive treatment.