HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J Appl Physiol 105: 1352-1358, 2008. First published May 8, 2008; doi:10.1152/japplphysiol.90423.2008
8750-7587/08 $8.00

This Article Free upon publication Full Text Free Full Text (PDF) Free All Versions of this Article: 105/4/1352    most recent 90423.2008v2 90423.2008v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Vimaleswaran, K. S. Articles by Franks, P. W. Search for Related Content PubMed PubMed Citation Articles by Vimaleswaran, K. S. Articles by Franks, P. W.

HIGHLIGHTED TOPIC
Physiology of the Aging Vasculature

The Gly482Ser genotype at the PPARGC1A gene and elevated blood pressure: a meta-analysis involving 13,949 individuals

¹Medical Research Council, Epidemiology Unit, Institute of Metabolic Science, Cambridge, United Kingdom; ²Steno Diabetes Center, Copenhagen, Denmark; ³National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona; ⁴Metabolic Disease Group, The Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, United Kingdom; ⁵Genetic Epidemiology and Clinical Research Group, Department of Public Health and Clinical Medicine, Division of Medicine, Umeå University Hospital, Umeå, Sweden; and ⁶Departments of Clinical Biochemistry and Medicine, Addenbrooke's Hospital, Cambridge, United Kingdom

Submitted 19 March 2008 ; accepted in final form 4 May 2008

The protein encoded by the PPARGC1A gene is expressed at high levels in metabolically active tissues and is involved in the control of oxidative stress via reactive oxygen species detoxification. Several recent reports suggest that the PPARGC1A Gly482Ser (rs8192678) missense polymorphism may relate inversely with blood pressure. We used conventional meta-analysis methods to assess the association between Gly482Ser and systolic (SBP) or diastolic blood pressures (DBP) or hypertension in 13,949 individuals from 17 studies, of which 6,042 were previously unpublished observations. The studies comprised cohorts of white European, Asian, and American Indian adults, and adolescents from South America. Stratified analyses were conducted to control for population stratification. Pooled genotype frequencies were 0.47 (Gly482Gly), 0.42 (Gly482Ser), and 0.11 (Ser482Ser). We found no evidence of association between Gly482Ser and SBP [Gly482Gly: mean = 131.0 mmHg, 95% confidence interval (CI) = 130.5–131.5 mmHg; Gly482Ser mean = 133.1 mmHg, 95% CI = 132.6–133.6 mmHg; Ser482Ser: mean = 133.5 mmHg, 95% CI = 132.5–134.5 mmHg; P = 0.409] or DBP (Gly482Gly: mean = 80.3 mmHg, 95% CI = 80.0–80.6 mmHg; Gly482Ser mean = 81.5 mmHg, 95% CI = 81.2–81.8 mmHg; Ser482Ser: mean = 82.1 mmHg, 95% CI = 81.5–82.7 mmHg; P = 0.651). Contrary to previous reports, we did not observe significant effect modification by sex (SBP, P = 0.966; DBP, P = 0.715). We were also unable to confirm the previously reported association between the Ser482 allele and hypertension [odds ratio: 0.97, 95% CI = 0.87–1.08, P = 0.585]. These results were materially unchanged when analyses were focused on whites only. However, statistical evidence of gene-age interaction was apparent for DBP [Gly482Gly: 73.5 (72.8, 74.2), Gly482Ser: 77.0 (76.2, 77.8), Ser482Ser: 79.1 (77.4, 80.9), P = 4.20 x 10^–12] and SBP [Gly482Gly: 121.4 (120.4, 122.5), Gly482Ser: 125.9 (124.6, 127.1), Ser482Ser: 129.2 (126.5, 131.9), P = 7.20 x 10^–12] in individuals <50 yr (n = 2,511); these genetic effects were absent in those older than 50 yr (n = 5,088) (SBP, P = 0.41; DBP, P = 0.51). Our findings suggest that the PPARGC1A Ser482 allele may be associated with higher blood pressure, but this is only apparent in younger adults.

meta-analysis; gene-environment interaction