Buraczynska Kinga, Koziol-Montewka Maria, Majdan Maria, Ksiazek Andrzej
Department of Medical Microbiology, Skubiszewski Medical University, Lublin, Poland.
Mol Diagn. 2003;7(3-4):175-80. doi: 10.1007/BF03260035.
Analyzing the molecular variants of immunological system genes helps to develop our understanding of the pathogenesis of several diseases. The tumor necrosis factor (TNF) is an important cytokine of cellular response and inflammation. The TNF gene is located within the MHC region on chromosome 6p21.3. Single nucleotide polymorphisms in the TNF gene, such as the one at a position -308, probably have a direct influence on TNF production. Myeloperoxidase, a heme enzyme, participates in micro-organism killing. The myeloperoxidase (MPO) gene is located on chromosome 17. In the promoter region, at position -463, G to A transition has been found, which causes decreased gene expression.
The aim of our study was to analyze the genetic polymorphisms of the TNF and MPO genes in patients with chronic renal failure.
The study included 95 patients with chronic renal failure and 115 healthy individuals. All participants were genotyped for TNF-308 and MPO promoter region polymorphisms by PCR, followed by digestion and gel electrophoresis. Genotype distribution was compared between patients and controls. For statistical analysis the Statistica PL 6.0 program was used. The Kruskal-Wallis and median test were employed; to evaluate relationship between quantitative data chi-square test was used.
There were no significant differences in genotype distribution of TNF or MPO polymorphisms between patients and controls. Some differences may be associated with gender because the TNF1/TNF1 genotype was significantly more common in healthy women in comparison with women with chronic renal failure (p < 0.05). In men, no such differences were found. For MPO polymorphism, in men with renal failure the GG genotype was significantly more frequent than in healthy men (p < 0.05). Comparing the MPO genotype distribution in diabetic nephropathy patients and nondiabetic patients, we found a statistically significant difference: GG and AA genotypes were more frequent in diabetic nephropathy than in other renal diseases (73 versus 60% and 10.8 versus 1.7%, respectively; p < 0.05). The genotype distribution in patients with other renal diseases was similar to the control group. There was a correlation between the TNF genotype and the age of onset of glomerulonephritis. For myeloperoxidase, there was a significant association between genotype and the age of onset of renal disease. There was no relationship between the TNF and MPO genotypes and time to end-stage renal disease.
Our studies show that the TNF and MPO genes may play a role in chronic renal failure. The relationship observed between polymorphisms of the TNF and MPO genes and chronic renal failure may depend on the pathophysiological changes in different diseases underlying renal failure.
分析免疫系统基因的分子变异有助于加深我们对多种疾病发病机制的理解。肿瘤坏死因子（TNF）是细胞反应和炎症的一种重要细胞因子。TNF基因位于6号染色体p21.3的主要组织相容性复合体（MHC）区域内。TNF基因中的单核苷酸多态性，如位于-308位置的多态性，可能对TNF的产生有直接影响。髓过氧化物酶是一种血红素酶，参与杀灭微生物。髓过氧化物酶（MPO）基因位于17号染色体上。在启动子区域，已发现-463位置存在G到A的转变，这会导致基因表达降低。
我们研究的目的是分析慢性肾衰竭患者中TNF和MPO基因的遗传多态性。
该研究纳入了95例慢性肾衰竭患者和115名健康个体。所有参与者均通过聚合酶链反应（PCR）对TNF - 308和MPO启动子区域多态性进行基因分型，随后进行酶切和凝胶电泳。比较患者和对照组之间的基因型分布。统计分析使用Statistica PL 6.0程序。采用Kruskal - Wallis检验和中位数检验；为评估定量数据之间的关系使用卡方检验。
患者和对照组之间TNF或MPO多态性的基因型分布无显著差异。一些差异可能与性别有关，因为与慢性肾衰竭女性相比，健康女性中TNF1/TNF1基因型显著更常见（p < 0.05）。在男性中未发现此类差异。对于MPO多态性，肾衰竭男性中GG基因型的频率显著高于健康男性（p < 0.05）。比较糖尿病肾病患者和非糖尿病患者的MPO基因型分布，我们发现了统计学上的显著差异：糖尿病肾病患者中GG和AA基因型比其他肾脏疾病患者更常见（分别为73%对60%和10.8%对1.7%；p < 关于其他肾脏疾病患者的基因型分布与对照组相似。TNF基因型与肾小球肾炎的发病年龄之间存在相关性。对于髓过氧化物酶，基因型与肾脏疾病的发病年龄之间存在显著关联。TNF和MPO基因型与终末期肾病的时间之间没有关系。
我们的研究表明，TNF和MPO基因可能在慢性肾衰竭中起作用。观察到的TNF和MPO基因多态性与慢性肾衰竭之间的关系可能取决于肾衰竭潜在不同疾病的病理生理变化。
