TCF7L2 Polymorphism rs7903146 Is Associated with Coronary Artery Disease Severity and Mortality

被引:54
作者
Sousa, Andre Gustavo P.
Marquezine, Guilherme F.
Lemos, Pedro A.
Martinez, Eulogio
Lopes, Neuza
Hueb, Whady A.
Krieger, Jose E.
Pereira, Alexandre C.
机构
[1] Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of São Paulo Medical School, São Paulo
[2] Clinical Medicine Department, Federal University of Rio Grande do Norte, Natal
[3] Hemodynamic Laboratory, Heart Institute (InCor), University of São Paulo Medical School, São Paulo
[4] Coronary Artery Disease Service, Heart Institute (InCor), University of São Paulo Medical School, São Paulo
关键词
CARDIOVASCULAR-DISEASE; ATHEROSCLEROSIS RISK; CANCER RISK; MASS-II; POPULATION; VARIANT; HYPERGLYCEMIA; ANGIOPLASTY; MEDICINE; SURGERY;
D O I
10.1371/journal.pone.0007697
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Background: TCF7L2 polymorphisms have been consistently associated with type 2 diabetes mellitus in different populations and type 2 diabetes mellitus is a major risk factor for cardiovascular disease, especially coronary artery disease. This study aimed to evaluate the association between TCF7L2 polymorphism rs7903146 and coronary artery disease in diabetic and non-diabetic subjects. Methods and Results: two populations were studied in order to assess severity of coronary artery disease and cardiovascular events incidence. Eight-hundred and eighty nine subjects who were referred for cardiac catheterization for coronary artery disease diagnosis were cross-sectionally evaluated for coronary lesions (atherosclerotic burden) and 559 subjects from the MASS-II Trial were prospectively followed-up for 5 years and assessed for major cardiovascular events incidence. As expected, rs7903146 T allele was associated with diabetes. Although diabetic patients had a higher prevalence of coronary lesions, no association between TCF7L2 genotype and coronary lesions was found in this subgroup. However, non-diabetic individuals carrying the T allele were associated with a significantly higher frequency of coronary lesions than non-diabetic non-carriers of the risk allele (adjusted OR = 2.32 95% CI 1.27-4.24, p = 0.006). Moreover, presence of multi-vessel coronary artery disease was also associated with the CT or TT genotypes in non-diabetics. Similarly, from the prospective sample analysis, non-diabetics carrying the CT/TT genotypes had significantly more composite cardiovascular end-points events than CC carriers (p = 0.049), mainly due to an increased incidence of death (p = 0.004). Conclusions: rs7903146 T allele is associated with diabetes and, in non-diabetic individuals, with a higher prevalence and severity of coronary artery disease and cardiovascular events. name of registry site (see list below), registration number, trial registration URL in brackets.
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页数:7
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