PGC-1alpha Gly482Ser polymorphism associates with hypertension among Danish whites.
PGC-1alpha is a coactivator of numerous transcription factors and is expressed in tissues with high energy demands and abundant in mitochondria. It is induced in the myocardium on fasting and physical exercise, and cardiac-specific overexpression stimulates mitochondrial biogenesis in mice. The common Gly482Ser polymorphism of PGC-1alpha has previously shown association with arterial hypertension among Austrian men. Thus, we aimed at investigating this relationship in the Danish white population. The Gly482Ser polymorphism was genotyped in a total of 2562 Danish white subjects using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) and a GenoView locked nucleic acid assay (LNA), and the relationships of this variant with blood pressure levels and arterial hypertension were analyzed. Furthermore, we performed a combined analysis of the data from the present study in combination with previously published results. The Ser/Ser genotype was significantly associated with a reduced risk of hypertension and with lower systolic, diastolic, and mean arterial blood pressure levels, predominantly among women. Finally, in a combined analysis using data obtained in both sexes, the Ser/Ser genotype group had an estimated odds ratio of 0.70 (95% confidence interval, 0.56 to 0.86) for hypertension compared with Gly/X carriers (P=0.001). In conclusion, the Ser allele of PGC-1alpha Gly482Ser confers a significantly reduced risk of hypertension in whites. Further studies are needed to elucidate the differential role of this polymorphism in men and women.
Andersen
Gitte
G
Steno Diabetes Center, Niels Steensens Vej 2, NSH2.16, DK-2820 Gentofte, Denmark. gtta@steno.dk
Wegner
Lise
L
Jensen
Dorit Packert
DP
Glümer
Charlotte
C
Tarnow
Lise
L
Drivsholm
Thomas
T
Poulsen
Pernille
P
Hansen
Sara Kristine
SK
Nielsen
Eva-Maria Damsgaard
EM
Ek
Jakob
J
Mouritzen
Peter
P
Vaag
Allan
A
Parving
Hans-Henrik
HH
Borch-Johnsen
Knut
K
Jørgensen
Torben
T
Hansen
Torben
T
Pedersen
Oluf
O
D000328:Adult; D000368:Aged; D001794:Blood Pressure; D003718:Denmark; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005998:Glycine; D006360:Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D006973:Hypertension / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012306:Risk; D012694:Serine; D012727:Sex Characteristics; D014157:Transcription Factors / Q000235:genetics*; D044465:White People / Q000235:genetics*
D006360:Heat-Shock Proteins; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors; D012694:Serine; D005998:Glycine