The impact of severity of hypertension on association of PGC-1alpha gene with blood pressure and risk of hypertension.
BACKGROUND
Little is known about the impact of severity of hypertension on the association of genes with high blood pressure, which may cause the inconsistently reported associations of peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) gene with blood pressure.


METHODS
A cardiovascular epidemiology survey and genotyping were performed in a population-based sample of 1642 apparently healthy residents (648 men and 994 women aged 35-91 years).


RESULTS
After adjusting for age, sex, body mass index, and antihypertensive medication, G482S and +2962A/G polymorphisms were significantly associated with systolic blood pressures in hypertension patients with medication use (p = 0.023 and 0.022 for G482S and +2962A/G respectively) but not in all participants, normotensives, and patients with no medication use. Multivariable logistic models showed that the two polymorphisms were significantly associated with severe hypertension (SBP > or = 160 mm Hg or DBP > or = 100 mm Hg regardless of medication use), with an OR of 0.6(95% confidence interval [CI]: 0.4-0.98) for S482S vs. G482G and an OR of 1.9(95% CI: 1.2-3.0) for +2962G/G vs. +2962A/A, but not with regular hypertension (SBP > or = 140 mm Hg or DBP > or = 90 mm Hg or current use of antihypertensive medications), with an OR of 0.9(95% CI: 0.7-1.2) for S482S vs. G482G and an OR of 0.9(95% CI: 0.7-1.4) for +2962G/G vs. +2962A/A. Haplotype combination analyses showed a significant synthetic effect (OR of severe hypertension for persons with G482X and +2962G/G = 2.6, 95%CI: 1.5-4.4, with reference to persons with S482S and +2962A/X).


CONCLUSIONS
In this study, we found that G482S and +2962A/G polymorphisms of PGC-1alpha gene were only significantly associated with severe hypertension defined by occasional clinic blood pressure measurements. This finding suggested severe hypertension rather than regular hypertension should be used as the outcome in studies on association of genes with blood pressure or hypertension, in order to have a better power.
Xie
Gaoqiang
G
Department of Epidemiology, Cardiovascular Institute and Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, The National Center for Cardiovascular Disease Control and Research, China. gqxie72@163.com
Guo
Dongshuang
D
Li
Ying
Y
Liang
Shengying
S
Wu
Yangfeng
Y
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001794:Blood Pressure / Q000235:genetics*; D002681:China / Q000453:epidemiology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006360:Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D006973:Hypertension / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011159:Population Surveillance; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D014157:Transcription Factors / Q000235:genetics*
D006360:Heat-Shock Proteins; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors