A polymorphism in the promoter of the tumor necrosis factor-alpha gene (-308) is associated with coronary heart disease in type 2 diabetic patients.
BACKGROUND
Tumor necrosis factor-alpha (TNF-alpha) is a key cytokine in the inflammation process of atherosclerosis. Through its effects on lipid metabolism, insulin resistance and endothelial function, it might be involved in coronary heart disease (CHD). A biallelic polymorphism within the promoter of TNF-alpha locus at the position -308 has been reported to be associated with TNF production. We have studied the association of this polymorphism with CHD in a Mediterranean non-diabetic and type 2 diabetic population.


METHODS
Three hundred and forty one CHD patients (106 with type 2 diabetes), 207 healthy matched control subjects and 135 type 2 diabetic patients without CHD were evaluated. A single nucleotide polymorphism at the promoter TNF-alpha (-308) was analyzed by RFLP-PCR.


RESULTS
TNF-alpha (-308) genotype and allele frequencies for A carriers were higher in CHD patients than those observed in the control group (32.3 vs. 23.2%, P=0.03; and 18.8 vs. 12.1%, P=0.0047; respectively) independently of other risk factors. Genotypic analysis revealed that CHD patients with type 2 DM displayed a greater prevalence of the -308 TNF-alpha A allele (40.6%) than controls (23.2%) or CHD patients without type 2 DM (28.5%) (P=0.0056). The odds ratio for CHD in type 2 diabetic patients in presence of -308 TNF-alpha A allele was 2.86 (CI 95%: 1.55-5.32). This difference was observed mainly in diabetic women for the A allele carriers (OR: 4.29; CI 95%: 1.6-11.76).


CONCLUSIONS
These results suggest that -308 TNF-alpha gene polymorphism may contribute to CHD risk in patients with type 2 diabetes and it could constitute an useful predictive marker for CHD in type 2 diabetic women.
Vendrell
Joan
J
Endocrinology Unit, Internal Medicine Service, Tarragona, Spain. jvo@comt.es
Fernandez-Real
José Manuel
JM
Gutierrez
Cristina
C
Zamora
Alberto
A
Simon
Inmaculada
I
Bardaji
Alfredo
A
Ricart
Wifredo
W
Richart
Cristobal
C
D017677:Age Distribution; D016022:Case-Control Studies; D015331:Cohort Studies; D015897:Comorbidity; D016001:Confidence Intervals; D003327:Coronary Disease / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis / Q000453:epidemiology*; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D015994:Incidence; D016015:Logistic Models; D008297:Male; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011237:Predictive Value of Tests; D011336:Probability; D011379:Prognosis; D011401:Promoter Regions, Genetic; D012016:Reference Values; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D017678:Sex Distribution; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D005819:Genetic Markers; D014409:Tumor Necrosis Factor-alpha