Association of genetic variants with the metabolic syndrome in 20,806 white women: The Women's Health Genome Study.
BACKGROUND
Candidate genes associated with cardiovascular disease (CVD) represent potential risk factors for the metabolic syndrome (MetS).


METHODS
The association between prevalent MetS and a panel of 62 polymorphisms within 42 candidate genes, previously implicated in the pathophysiology of CVD, were investigated in 20,806 white participants of the Women's Health Study. All were free of known CVD and diabetes at baseline. Logistic regression was performed to investigate the relationship between genotype and the MetS assuming an additive model. Stratified analyses by hormone therapy use were also performed. Correction for multiple testing was performed using false discovery rate for polymorphisms and false positive rate probability for stratified analysis, respectively.


RESULTS
The prevalence of the MetS was 23%. In a marker-by-marker analysis, the ADRB2 rs180088 (OR 1.22, 95% CI 1.01-1.48) and PAI1 rs1799768 (OR 1.05, 95% CI 1.01-1.10) were associated with an increased MetS risk, whereas the C5 rs17611 (OR 0.95, 95% CI 0.91-1.00) and the CTLA4 rs5742909 (OR 0.91, 95% CI 0.84-0.99) were associated with a decreased risk. In postmenopausal women, an increased MetS risk was found for the ADRB2 rs180088 (OR 1.28, 95% CI 0.99-1.65), PAI1 rs1799768 (OR 1.07, 95% CI 1.01-1.14), SCNN1A rs5742912 (OR 1.22, 95% CI 1.01-1.47), and IL1A rs1800587 (OR 1.07, 95% CI 1.01-1.15), whereas the AGTR1 rs5186 (OR 0.93, 95% CI 0.87-0.99) was associated with decreased risk. However, none remained significant after false discovery rate correction. In a stratified analysis, one or more copies of the variant C allele of SCNN1A rs5742912 were associated with an increased MetS risk among the current users (OR 1.56, 95% CI 1.21-2.01, P interaction .007, false positive rate probability 0.13).


CONCLUSIONS
Effect modification of the SCNN1A rs5742912 on the MetS by hormone therapy use warrants further investigation.
Goulart
Alessandra C
AC
Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA.
Rexrode
Kathryn M
KM
Cheng
Suzanne
S
Rose
Lynda
L
Buring
Julie E
JE
Ridker
Paul M
PM
Zee
Robert Y L
RY
D000368:Aged; D000369:Aged, 80 and over; D003925:Diabetic Angiopathies / Q000235:genetics; D053503:Epithelial Sodium Channels / Q000235:genetics*; D005260:Female; D005838:Genotype; D020249:Hormone Replacement Therapy; D006801:Humans; D024821:Metabolic Syndrome / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic
D053503:Epithelial Sodium Channels; C507045:SCNN1A protein, human