Impact of cytokine genotype on cardiovascular surrogate markers in hemodialysis patients.
OBJECTIVE
Cytokine gene polymorphisms have been implicated as potential genetic risk factors for cardiovascular diseases (CVDs). Atherosclerosis and left ventricular hypertrophy (LVH) are surrogate markers for CVDs in uremic patients. The aim of this study was to assess the role of cytokine gene polymorphisms in carotid intima-media thickness (CIMT) and left ventricular mass index (LVMI) progression in nondiabetic hemodialysis (HD) patients.


METHODS
About 102 nondiabetic patients on maintenance HD were included in this study. Patients were followed up for 2 years. Genetic polymorphisms of TNF-alpha (-308 G/A, -238A/G) and IL-10 (-1082 A/G, -819 C/T, -592 A/C) were determined by polymerase chain reaction. Biochemical parameters and inflammatory markers and ambulatory blood pressure (BP) measurements were determined during the study period. CIMT and LVMI were also determined at baseline and after the first and second year.


RESULTS
Cardiovascular risk factors did not differ between TNF-alpha -308 high-/low-producer genotype groups. However, CIMT and LVMI progression were detected at higher levels in patients with high-producer genotypes (AA+AG) than in patients with the low-producer genotype (GG) during the study period. The TNF-alpha -308 G/A polymorphism was closely associated with C-reactive protein (CRP), a marker of systemic inflammation in the study population. Analysis also showed that the combination of high production of TNF-alpha and low production of IL-10 was associated with higher average IMT and LVMI progression and elevated average CRP levels compared with a combination of low production of TNF-alpha and high production of IL-10.


CONCLUSIONS
Polymorphisms in inflammatory genes may represent an additional factor affecting inflammation and CVD progression in nondiabetic HD patients.
Yilmaz
Rahmi
R
Department of Nephrology, Faculty of Medicine, Hacettepe University, Ankara, Turkey. drrahmiy@hotmail.com
Altun
Bulent
B
Ozer
Necla
N
Hazirolan
Tuncay
T
Turgan
Cetin
C
D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood* / Q000235:genetics*; D002339:Carotid Arteries / Q000473:pathology; D005260:Female; D005838:Genotype; D006352:Heart Ventricles / Q000473:pathology; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D006435:Renal Dialysis; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D017539:Tunica Intima / Q000473:pathology; D017540:Tunica Media / Q000473:pathology
D015415:Biomarkers; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10