TY - JOUR

T1 - PGC-1alpha Gly482Ser polymorphism associates with hypertension among Danish whites

AU - Andersen, Gitte

AU - Wegner, Lise

AU - Jensen, Dorit Packert

AU - Glümer, Charlotte

AU - Tarnow, Lise

AU - Drivsholm, Thomas

AU - Poulsen, Pernille

AU - Hansen, Sara Kristine

AU - Nielsen, Eva-Maria Damsgaard

AU - Ek, Jakob

AU - Mouritzen, Peter

AU - Vaag, Allan

AU - Parving, Hans-Henrik

AU - Borch-Johnsen, Knut

AU - Jørgensen, Torben

AU - Hansen, Torben

AU - Pedersen, Oluf

PY - 2005/4/1

Y1 - 2005/4/1

N2 - 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.

AB - 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.

KW - Adult

KW - Aged

KW - Blood Pressure

KW - Denmark

KW - European Continental Ancestry Group

KW - Female

KW - Genetic Predisposition to Disease

KW - Genotype

KW - Glycine

KW - Heat-Shock Proteins

KW - Humans

KW - Hypertension

KW - Male

KW - Middle Aged

KW - Polymorphism, Genetic

KW - Polymorphism, Restriction Fragment Length

KW - Reverse Transcriptase Polymerase Chain Reaction

KW - Risk

KW - Serine

KW - Sex Characteristics

KW - Transcription Factors

U2 - 10.1161/01.HYP.0000158946.53289.24

DO - 10.1161/01.HYP.0000158946.53289.24

M3 - Journal article

C2 - 15738346

VL - 45

SP - 565

EP - 570

JO - Hypertension

JF - Hypertension

SN - 0194-911X

IS - 4

ER -