Relationship between two sequence variations in the gene for peroxisome proliferator-activated receptor-gamma and plasma homocysteine concentration. Health in men study

Golledge, Jonathan, and Norman, Paul E. (2008) Relationship between two sequence variations in the gene for peroxisome proliferator-activated receptor-gamma and plasma homocysteine concentration. Health in men study. Human Genetics, 123 (1). pp. 35-40.

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Abstract

The concentration of circulating homocysteine has been associated with a variety of diseases, including myocardial infarction, stroke, venous thrombosis and cognitive decline. Genetic variation has been demonstrated to play an important role in determining plasma homocysteine, however, the genes involved are incompletely understood. Ligation of the transcription factor peroxisome proliferator-activated gamma (PPARG) has been demonstrated to lower plasma homocysteine. We examined the association of two sequence variations in PPARG with plasma concentrations of homocysteine in a population-based study of 3,875 elderly men. PPARG c.34G > C and PPARG c.1347C > T sequence variations were determined by real-time quantitative PCR and related to logarithm transformed homocysteine concentrations using linear regression, adjusting for the co-variants age, renal function, smoking, coronary heart disease, waist to hip ratio, diabetes, hypertension and MTHFR g.677C > T sequence variation. Median plasma homocysteine concentration was 10% higher in men who were homozygous for the rare allelic variation in PPARG c.34G > C and PPARG c.1347C > T by comparison to those who had wild type sequence variation. PPARG c.1347C > T (β = 0.038, P = 0.01 recessive model; β = 0.036, P = 0.02 dominant model) sequence variation was positively associated with homocysteine concentration after adjusting for co-variants. The two PPARG sequence variations were in linkage disequilibrium and the common haplotype was associated with lower plasma homocysteine (P = 0.005). Our findings demonstrate a new genotypic association with plasma homocysteine. Replication will be required in other cohorts.

Item ID: 6391
Item Type: Article (Refereed Research - C1)
Keywords: plasma homocysteine; genetic variation in PPARG; mens health; homocysteine; PPARG; peroxisome proliferator-activated gamma
ISSN: 1432-1203
Date Deposited: 22 Jan 2010 00:04
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1102 Cardiovascular Medicine and Haematology > 110201 Cardiology (incl Cardiovascular Diseases) @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920103 Cardiovascular System and Diseases @ 67%
92 HEALTH > 9205 Specific Population Health (excl. Indigenous Health) > 920505 Mens Health @ 33%
Citation Count from Web of Science Web of Science 5
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