Altun Bülent, Yilmaz Rahmi, Kahraman Serkan, Gençtoy Gültekin, Arici Mustafa, Onalan Orhan, Oto Aytekin, Hayran Mutlu, Bakkaloğlu Mehmet, Yasavul Unal, Turgan Cetin
Division of Nephrology, Department of Internal Medicine, Hacettepe University Faculty of Medicine, Sihhiye, Ankara, Turkey.
Transpl Int. 2005 Jun;18(6):681-9. doi: 10.1111/j.1432-2277.2005.00118.x.
Cardiovascular events are the leading causes of morbidity and mortality in renal transplant recipients (RTR). Given the role of inflammation in atherosclerosis, the contribution of functional polymorphisms of cytokines to cardiovascular diseases (CVD) was assessed in RTR in this study. Polymorphisms of tumour necrosis factor alpha (TNF-alpha) gene [-308 (G-->A), -238 (G-->A)], interleukin-10 (IL-10) gene [-1082(A-->G), -819 (T-->C), -592 (A-->C)], transforming growth factor beta 1 (TGF-beta1) gene [codon 10 (T-->C), codon 25 (G-->C)], carotis intima media thickness (CIMT), left ventricular mass index (LVMI), 24-h ambulatory blood pressure and serum lipoprotein homocysteine level, erythrocyte sedimentation rate, serum C-reactive protein (CRP) and serum fibrinogen level of RTR were determined. Seventy-two RTR (26 cadaveric allograft, 46 living-related allograft, 43 male, 29 female) were included in this study. LVMI were similar in TNF-alpha, IL-10 and TGF-beta1 genotypes. Right and left CIMT were higher in TT genotype (n = 16) than CT (n = 46) and CC (n = 10) genotypes of TGF-beta1 codon 10 (T-->C) gene polymorphism (RCIMT, 7.7 +/- 2.2 mm vs. 7.0 +/- 1.4 mm vs. 5.9 +/- 1.4 mm, P = 0.025; LCIMT, 8.5 +/- 2.5 mm vs. 7.0 +/- 1.3 mm vs. 6.1 +/- 1.2 mm, P = 0.002). Lipoprotein (a) level of TT genotype (35.5 +/- 22.5 mg/dl) was higher than CC (4.1 +/- 2.8 mg/dl) and CT (20.4 +/- 11.2 mg/dl) genotypes of TGF-beta1 codon 10 (T-->C) gene polymorphism (P = 0.037). High producers of cytokine IL-10 -1082 [GG (n = 22) vs. AA + AG (n = 50)] and low producers of TGF-beta codon 25 [GC + CC (n = 17) vs. GG (n = 55)] had lower IMT of carotid artery but the difference did not reach statistical significance (P > 0.05). The CIMT of renal transplant patients was similar in IL-10 (-819, -592) and TNF-alpha (-308, -238) genotypes. No difference was observed in 24-h ambulatory blood pressure levels, serum lipoproteins, plasma homocysteine level, erythrocyte sedimentation rate, serum CRP, serum fibrinogen level in IL-10, TNF-alpha and TGF-beta1 genotypes. Besides the well-known factors, TGF-beta1 gene polymorphisms might play a role in CVD in RTR even at early stages of asymptomatic atherosclerosis.
心血管事件是肾移植受者（RTR）发病和死亡的主要原因。鉴于炎症在动脉粥样硬化中的作用，本研究评估了细胞因子功能多态性对RTR心血管疾病（CVD）的影响。检测了肿瘤坏死因子α（TNF-α）基因[-308（G→A）、-238（G→A）]、白细胞介素-10（IL-10）基因[-1082（A→G）、-819（T→C）、-592（A→C）]、转化生长因子β1（TGF-β1）基因[密码子10（T→C）、密码子25（G→C）]的多态性，以及RTR的颈动脉内膜中层厚度（CIMT）、左心室质量指数（LVMI）、24小时动态血压、血清脂蛋白同型半胱氨酸水平、红细胞沉降率、血清C反应蛋白（CRP）和血清纤维蛋白原水平。本研究纳入了72例RTR（26例尸体同种异体移植、46例亲属活体同种异体移植、43例男性、29例女性）。LVMI在TNF-α、IL-10和TGF-β1基因型中相似。TGF-β1密码子10（T→C）基因多态性的TT基因型（n = 16）的左右CIMT高于CT基因型（n = 46）和CC基因型（n = 10）（右侧CIMT，7.7±2.2mm对7.0±1.4mm对5.9±1.4mm，P = 0.025；左侧CIMT，8.5±2.5mm对7.0±1.3mm对6.1±1.2mm，P = 0.002）。TGF-β1密码子10（T→C）基因多态性的TT基因型（35.5±22.5mg/dl）的脂蛋白（a）水平高于CC基因型（4.1±2.8mg/dl）和CT基因型（20.4±11.2mg/dl）（P = 0.037）。细胞因子IL-10 -1082的高产生者[GG（n = 22）对AA + AG（n = 50）]和TGF-β密码子25的低产生者[GC + CC（n = 17）对GG（n = 55）]的颈动脉内膜中层厚度较低，但差异未达到统计学意义（P>0.05）。肾移植患者的CIMT在IL-10（-819、-592）和TNF-α（-308、-238）基因型中相似。在IL-10-TNF-α和TGF-β1基因型的24小时动态血压水平、血清脂蛋白、血浆同型半胱氨酸水平、红细胞沉降率、血清CRP、血清纤维蛋白原水平方面未观察到差异。除了众所周知的因素外，即使在无症状动脉粥样硬化的早期阶段，TGF-β1基因多态性可能在RTR的CVD中起作用。
