Kusztal M, Radwan-Oczko M, Kościelska-Kasprzak K, Boratyńska M, Patrzałek D, Klinger M
Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Wroclaw, Poland.
Transplant Proc. 2007 Nov;39(9):2763-5. doi: 10.1016/j.transproceed.2007.09.002.
T-lymphocytes may play a role in the pathogenesis of inflammatory periodontal diseases and cyclosporine (CsA)-induced gingival overgrowth (GO). The gene encoding CTLA-4 (Cytotoxic T-lymphocyte antigen 4, a molecule influencing T-cell activation), is known to have a single nucleotide polymorphism (SNP) in promoter C>T -318; an exon 1 A>G 49, and a microsatellite dinucleotide repeat polymorphism (AT)(n) in exon 4. The purpose of this study was to analyze the possible influence of polymorphisms of CTLA-4, interleukin (IL)-2, and tumor necrosis factor (TNF)-alpha on GO incidence in eighty two renal transplant recipients. 34 CsA-treated with significant GO (CsAGO+); 22, CsA-treated with no GO (CsAGO-), and 26 tacrolimus (Tac)-treated without GO (TacGO-). The SNPs of CTLA-4 (-318 C>T and +49 A>G), IL-2 (-330T>G), and TNF-alpha (-308 G>A) were determined by SSP-PCR methods. The CTLA-4 (AT)(n) genotype was determined using polymerase chain reaction and fluorescence-based analysis with capillary electrophoresis. Allele frequencies in all patient groups were similar for CTLA-4 -318C>T, IL-2, and TNF-alpha. However, patients with CsAGO+ showed differences from CsAGO- for allele and genotype frequencies in position +49A>G of the CTLA-4 gene. The +49G allele was two times less frequent among CsAGO+ than CsAGO- (P = .0052; P corrected = .008). Slight differences between CsAGO+ and CsAGO- were noticed for the genotype distribution of CTLA-4 (AT)(n) (P = .056). The results suggested that appearance of an adenosine allele(A) in position +49 of the CTLA-4 gene may be a permissive element for CsA-induced GO.
T淋巴细胞可能在炎症性牙周疾病和环孢素（CsA）诱导的牙龈过度生长（GO）的发病机制中起作用。已知编码CTLA-4（细胞毒性T淋巴细胞抗原4，一种影响T细胞活化的分子）的基因在启动子区域存在单核苷酸多态性（SNP）C>T -318；外显子1存在A>G 49，外显子4存在微卫星二核苷酸重复多态性（AT）(n)。本研究的目的是分析CTLA-4、白细胞介素（IL）-2和肿瘤坏死因子（TNF）-α基因多态性对82例肾移植受者中GO发生率的可能影响。34例接受CsA治疗且有明显GO（CsAGO+）；22例接受CsA治疗但无GO（CsAGO-），26例接受他克莫司（Tac）治疗且无GO（TacGO-）。通过序列特异性引物聚合酶链反应（SSP-PCR）方法测定CTLA-4（-318 C>T和+49 A>G）、IL-2（-330T>G）和TNF-α（-308 G>A）的SNP。使用聚合酶链反应和基于荧光的毛细管电泳分析确定CTLA-4（AT）(n)基因型。所有患者组中CTLA-4 -318C>T、IL-2和TNF-α的等位基因频率相似。然而，CsAGO+患者在CTLA-4基因+49A>G位置的等位基因和基因型频率与CsAGO-患者存在差异。CsAGO+中+49G等位基因的频率比CsAGO-低两倍（P = .0052；校正P = .008）。在CTLA-4（AT）(n)的基因型分布方面，CsAGO+和CsAGO-之间存在细微差异（P = .056）。结果表明，CTLA-4基因+49位出现腺苷等位基因（A）可能是CsA诱导GO的一个许可因素。
