Context: Recent genome-wide association studies have identified several single-nucleotide polymorphisms (SNPs) that are associated with body mass index (BMI)/obesity.
Objective: As obesity is an independent risk factor for hypertension, the objective of the study was to investigate the associations of obesity susceptibility loci with blood pressure (BP)/hypertension in a population of Chinese children.
Design, setting and participants: This was a genotype-phenotype association study. Participants included 3077 Chinese children, aged 6-18 years. Based on the Chinese age- and sex-specific BP standards, 619 hypertensive cases and 2458 controls with normal BP were identified.
Main outcome measures: BP was measured by auscultation using a standard clinical sphygmomanometer.
Results: Of the 11 SNPs, only FTO rs9939609 was significantly associated with systolic BP (SBP; P=0.034) and three SNPs were significantly associated with diastolic BP (DBP; GNPDA2 rs10938397: P=0.026; FAIM2 rs7138803: P=0.015; NPC1 rs1805081: P=0.031) after adjustment for age, sex and hypertension status. In addition, three SNPs were significantly associated with hypertension risk after adjustment for age and sex (FTO rs9939609: odds ratio (OR)=1.35, 95% confidence interval (CI) 1.12-1.62, P=0.001; MC4R rs17782313: OR=1.22, 95% CI 1.06-1.42, P=0.007; GNPDA2 rs10938397: OR=1.17, 95% CI 1.02-1.34, P=0.021). After additional adjustment for BMI, none remained significant. The genetic risk score (GRS), based on three significant SNPs (FTO rs9939609, MC4R rs17782313, GNPDA2 rs10938397), showed a positive association with SBP (P=5.17 × 10(-4)) and risk of hypertension (OR=1.22, 95% CI 1.12-1.33, P=6.07 × 10(-6)). Further adjustment for BMI abolished the positive associations (SBP: P=0.220; DBP: P=0.305; hypertension: P=0.052). Only FTO rs9939609 and GRS were statistically associated with hypertension risk in the age- and sex-adjusted model after correction for multiple testing.
Conclusions: The present study demonstrated that FTO rs9939609 and combined SNPs were significantly associated with risk of hypertension, which seems to be dependent on BMI.