Gender-Specific Association Between FGFR4 Gly388Arg Gene Variants and Hypertension

Variations in fibroblast growth factor (FGF) levels have been associated with alterations in blood pressure. FGFs mediate their function through binding to their FGF receptor (FGFR). The FGFR4 Gly388Arg polymorphism is associated with cancer and cardiovascular diseases, but its association with hypertension is unclear. Here, we aimed to investigate the association between the FGFR4 Gly388Arg polymorphism and hypertension.Three hundred Saudi individuals (150 normotensive controls and 150 hypertensive subjects) were genotyped for the FGFR4 Gly388Arg (G/A) polymorphism using polymerase chain reaction-restriction fragment length polymorphism method. Anthropometrics, glucose and lipid profiles were measured for all subjects. The frequency of the FGFR4 Arg388 (A) allele was significantly higher in hypertensive subjects (36%) than controls (24.3%) (odds ratio [OR] 2.4, 95% confidence interval [CI] 1.5-3.83, p < 0.001). In addition, GA (OR 2.51, 95% CI 1.3-4.85, p = 0.006), AA (OR 5.58, 95% CI 1.79-11.8, p = 0.003), and GA + AA (OR 2.91, 95% CI 1.55-5.46, p = 0.001) genotypes were significantly associated with the risk of hypertension, even after adjusting for age, body mass index, and glucose. Gender stratification showed a significant association only in female subjects (p < 0.001). Furthermore, subjects with GA and AA genotypes showed significantly higher diastolic blood pressure than those with GG genotype (p = 0.004).The FGFR4 Arg388 allele is associated with an increased risk of hypertension in Saudi female subjects. The lack of association in men needs to be further investigated.