Association of common variants in/near six genes (ATP2B1, CSK, MTHFR, CYP17A1, STK39 and FGF5) with blood pressure/hypertension risk in Chinese children

Abstract

Recent genome-wide association studies have identified several single-nucleotide polymorphisms (SNPs) that are associated with blood pressure (BP)/hypertension. In this study, we aimed to examine the established associations amongst Chinese children. We genotyped six SNPs (ATP2B1 rs17249754, CSK rs1378942, MTHFR rs1801133, CYP17A1 rs1004467, STK39 rs3754777 and FGF5 rs16998073) in Chinese children (N=3077, age range, 6-18 years). Based on the Chinese age- and sex-specific BP standards, 619 hypertensive cases and 2458 controls with normal BP were identified. Of the six SNPs, only ATP2B1 rs17249754 SNP was significantly associated with the risk of hypertension (allelic odds ratio (OR)=1.25, 95% confidence interval (CI): 1.08-1.44, P=0.003). Although all other SNPs showed a trend towards increasing the BP values and risk of hypertension, there was no statistically significant association after false discovery rate analysis. We calculated the weighted risk score using six SNPs, for systolic BP (SBP), diastolic BP (DBP) and hypertension. Each additional weighted risk score was associated with SBP by 1.18 mm Hg (95% CI=0.62-1.73, P<0.001), but not with the DBP (β=0.28, 95% CI=(-0.15)-0.74), and overall increased the risk of hypertension by 1.19-fold (95% CI=1.04-1.35, P=0.01). The present study confirmed the significant association of ATP2B1 rs17249754 with risk of hypertension among Chinese children, but failed to replicate the association of CSK rs1378942, MTHFR rs1801133, CYP17A1 rs1004467, STK39 rs3754777 and FGF5 rs16998073 with BP/risk of hypertension.

Association between the MTHFR C677T gene polymorphism and essential hypertension in South West Cameroon

“…These results are contrary to those obtained in Spain where the MTHFR TT genotype could predict the development of EH in males (Rodríguez-Esparragón et al, 2003). Our results confirm the fact that differences in ethnicity and geographical location could genetically predispose individuals to hypertension (Hong et al, 2010;Xi et al, 2014).…”

“…Further contrary results were found in a Japanese study that revealed that the risk of EH significantly increased in subjects with the 677CC genotype, whereas the C677T gene polymorphism contributed to lower blood pressure (Nakata et al, 1998). These controversial results have suggested that differences in ethnicity and geographical location could genetically predispose individuals to EH (Hong et al, 2010;Xi et al, 2014).…”

“…Identification of these susceptible genes is potentially useful to elucidate the complex genetic mechanisms of the disease. Recently, single nucleotide polymorphisms (SNPs) in some candidate genes have been proven to confer susceptibility to the disease in some but not all European and Asian countries (Hong et al, 2010;Liu et al, 2011;Xi et al, 2014). The C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene has been reported to be associated with hypertension by virtue of its role in catalyzing the formation of 5-methylenetetrahydrofolate, a co-substrate for the conversion of homocysteine to methionine.…”

FGF5 is a crucial regulator of hair length in humans

“…Similarly, the effect of minoxidil (Rogaine) on hair growth was also discovered as a side effect of patients taking this drug for hypertension (32,33). Common variants upstream of FGF5 have been implicated in three genome-wide association studies of blood pressure (3 × 10 −14 ≤ P ≤ 9 × 10 −25 ) (34-36) and replicated in independent cohorts (37,38). A mechanistic link between FGF5 variants associated with blood pressure and hair growth awaits further investigation.…”

The Plasma Membrane Calcium ATPasesand Their Role as Major New Players in Human Disease

“…Although the effects of ATP2B1 variants on systolic and diastolic blood pressure are small at around 1 mmHg (105), Levy et al (206) predicted the risk of developing hypertension to increase by 17 and 37% dependent on whether one or two respective alleles are affected. This finding of an association between ATP2B1 and hypertension is not just limited to adults as one study has determined that the ATP2B1 SNP rs2681472 is associated with an increased risk of hypertension in Chinese children (407), while the same SNP also predisposes Chinese women to early-onset preeclampsia during pregnancy (389). Using a gene-centric array in which~50,000 SNPs in 2,100 genes previously implicated in cardiovascular, metabolic, and inflammatory processes, Fontana et al (124) demonstrated a strong association between SNP rs12817819 in ATP2B1 and resistant hypertension, a condition in which raised blood pressure is not controlled despite the use of at least three antihypertensive drugs.…”