Obesity genotype score and cardiovascular risk in women with type 2 diabetes mellitus.
OBJECTIVE
To investigate the associations between obesity-predisposing genetic variants, cardiovascular biomarkers, and cardiovascular disease (CVD) risk in women with preexisting type 2 diabetes mellitus.


RESULTS
We genotyped polymorphisms at nine established obesity loci in 1,395 women with diabetes from the Nurses' Health Study: 449 women developed CVD, and 946 women did not develop CVD. A genetic risk score (GRS) was derived by summing risk alleles for each individual. Four polymorphisms (rs9939609 [FTO], rs11084753 [KCTD15], rs10838738 [MTCH2], and rs10938397 [GNPDA2]) showed nominally significant associations with CVD. The GRS combining all obesity loci was linearly related to CVD risk (P = 0.013 for trend). The odds ratio was 1.08 per risk allele (95% confidence interval, 1.02-1.15; P = 0.01) after adjustment for body mass index and other conventional risk factors. Women with the highest quartile of GRS had 53% (95% confidence interval, 6%-122%) increased CVD risk, compared with those in the lowest quartile of GRS (P = 0.024). In addition, a higher GRS was associated with lower adiponectin levels (P = 0.02). Further adjustment for body mass index and other covariates did not change the association (P = 0.006). A higher GRS was also correlated with lower levels of high-density lipoprotein (P = 0.01).


CONCLUSIONS
Obesity-predisposing variants may jointly affect CVD risk among women with diabetes.
He
Meian
M
Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA.
Cornelis
Marilyn C
MC
Franks
Paul W
PW
Zhang
Cuilin
C
Hu
Frank B
FB
Qi
Lu
L
D052242:Adiponectin / Q000097:blood; D000328:Adult; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood / Q000235:genetics* / Q000401:mortality; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics* / Q000401:mortality; D005260:Female; D020022:Genetic Predisposition to Disease; D006442:Glycated Hemoglobin / Q000378:metabolism; D006306:Health Surveys; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D008055:Lipids / Q000097:blood; D016015:Logistic Models; D026901:Membrane Transport Proteins / Q000235:genetics; D008875:Middle Aged; D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins / Q000235:genetics; D009765:Obesity / Q000097:blood / Q000150:complications / Q000235:genetics* / Q000401:mortality; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D015221:Potassium Channels / Q000235:genetics; D011506:Proteins / Q000235:genetics; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D014481:United States / Q000453:epidemiology
D052242:Adiponectin; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D015415:Biomarkers; D006442:Glycated Hemoglobin; D018836:Inflammation Mediators; D008055:Lipids; D026901:Membrane Transport Proteins; D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins; D015221:Potassium Channels; D011506:Proteins; C499918:ADIPOQ protein, human; C502207:MTCH2 protein, human; C517652:hemoglobin A1c protein, human; C526492:FTO protein, human