title: 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.
authors.affiliation: 1] Department of Epidemiology, Capital Institute of Pediatrics, Beijing, China [2] Department of Maternal and Child Health Care, School of Public Health, Shandong University, Jinan, China.
authors.forename: B
authors.initials: B
authors.lastname: Xi
authors.forename: Y
authors.initials: Y
authors.lastname: Shen
authors.forename: X
authors.initials: X
authors.lastname: Zhao
authors.forename: G R
authors.initials: GR
authors.lastname: Chandak
authors.forename: H
authors.initials: H
authors.lastname: Cheng
authors.forename: D
authors.initials: D
authors.lastname: Hou
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.forename: J
authors.initials: J
authors.lastname: Ott
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.forename: J
authors.initials: J
authors.lastname: Mi
mesh_terms: D000293:Adolescent; D044466:Asian People / Q000235:genetics*; D001794:Blood Pressure / Q000235:genetics*; D000081247:CSK Tyrosine-Protein Kinase; D002648:Child; D002681:China; D003430:Cross-Sectional Studies; D005260:Female; D051521:Fibroblast Growth Factor 5 / Q000235:genetics; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D053499:Plasma Membrane Calcium-Transporting ATPases / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D012306:Risk; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics; D019061:src-Family Kinases / Q000235:genetics
chemical_list: C506952:ATP2B1 protein, human; C496449:FGF5 protein, human; D051521:Fibroblast Growth Factor 5; C501892:CYP17A1 protein, human; D013254:Steroid 17-alpha-Hydroxylase; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; C000631346:CSK protein, human; D017346:Protein Serine-Threonine Kinases; C486409:STK39 protein, human; D053499:Plasma Membrane Calcium-Transporting ATPases