Association of interleukin-18 promoter polymorphism and atherosclerotic diseases in Chinese patients with diabetic nephropathy.
OBJECTIVE
Interleukin-18 (IL-18) is a pro-inflammatory cytokine and possibly plays an important role in the pathogenesis of cardiovascular disease. The relationship between two IL-18 gene polymorphisms, namely C-607A and G-137C, and cardiovascular disease in patients with diabetic nephropathy was examined.


METHODS
Two hundred and twenty patients (91 male) with diabetic nephropathy were studied. The IL-18 promoter genotypes were determined. All patients were then prospectively followed for the cardiovascular events. Cardiovascular mortality and all-cause mortality were also compared.


RESULTS
Mean age was 64.3 +/- 10.6 years; average follow up was 73.9 +/- 33.6 months. The frequencies of CC, CA and AA genotypes of the C-607A polymorphism were 25.5%, 48.2% and 26.8%, respectively; GG, GC and CC genotypes of the G-137C polymorphism were 71.8%, 25.0% and 3.2%, respectively. Neither of the polymorphisms were associated with the development of primary cardiovascular end-point. Cardiovascular survival was 84.8% and 70.6% at 60 months for GG and GC/CC genotypes of the G-137C polymorphism, respectively (P = 0.027); the corresponding actuarial survival was 69.0% and 54.8%, respectively (P = 0.053). However, the G-137C genotype was not an independent predictor of cardiovascular or actuarial survival after adjusting for confounders by multivariate analysis with the Cox model. The C-607A polymorphism had no significant effect on cardiovascular or actuarial survival.


CONCLUSIONS
The G-137C polymorphism of the IL-18 promoter is associated with the cardiovascular mortality, and a trend of association with all-cause mortality, in patients with diabetic nephropathy. The association, however, becomes insignificant after adjusting for confounding factors. Further studies are needed to test other genetic determinants of the association between systemic inflammation and cardiovascular disease in renal failure patients.
Szeto
Cheuk-Chun
CC
Department of Medicine and Therapeutics, Prince of Wales Hospital, Chinese University of Hong Kong, Shatin, Hong Kong, China. ccszeto@cuhk.edu.hk
Chow
Kai-Ming
KM
Poon
Peter Yam-Kau
PY
Kwan
Bonnie Ching-Ha
BC
Li
Philip Kam-Tao
PK
D000328:Adult; D000368:Aged; D050197:Atherosclerosis / Q000235:genetics*; D002097:C-Reactive Protein / Q000032:analysis; D002318:Cardiovascular Diseases / Q000401:mortality; D003928:Diabetic Nephropathies / Q000209:etiology / Q000235:genetics*; D005260:Female; D005838:Genotype; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D020382:Interleukin-18 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012307:Risk Factors
D002097:C-Reactive Protein; D006442:Glycated Hemoglobin; D020382:Interleukin-18; C517652:hemoglobin A1c protein, human