Genetic variants and mRNA expression levels of <i>KLF4</i> and <i>KLF5</i> with hypertension: A combination of case-control study and cohort study

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 <i>KLF4</i> and <i>KLF5</i> 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 <i>KLF4</i> and three SNPs in <i>KLF5</i> 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 <i>KLF4</i> and <i>KLF5</i> 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 <i>KLF5</i> 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 <i>KLF5</i> 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). <i>KLF4</i> and <i>KLF5</i> mRNA expression levels were significantly higher in the AHD(-) group than in the control group ( <i>P</i> < 0.05), but lower in the AHD(+) group than in the AHD(-) group ( <i>P</i> < 0.05). The current study demonstrated the associations of <i>KLF4</i> and <i>KLF5</i> genetic variants with hypertension, as well as the association of the indicative variations in mRNA expression levels of <i>KLF4</i> and <i>KLF5</i> with the risk of hypertension and antihypertensive treatment.