Yigit Serbülent, Tural Sengul, Tekcan Akın, Tasliyurt Turker, Inanir Ahmet, Uzunkaya Süheyla, Kismali Gorkem
Gaziosmanpaşa University, Faculty of Medicine, Department of Medical Biology, Tokat, Turkey.
Ondokuz Mayis University, Faculty of Medicine, Department of Medical Biology and Genetics, Section of Medical Genetics, Samsun, Turkey.
Cytokine. 2014 May;67(1):1-6. doi: 10.1016/j.cyto.2014.01.007. Epub 2014 Feb 22.
Familial Mediterranean fever (FMF) is characterized by recurrent attacks of fever and inflammation in the peritoneum, synovium, or pleura, accompanied by pain. It is an autosomal recessive disease caused by mutations in the MEFV (MEditerranean FeVer) gene. Patients with similar genotypes exhibit phenotypic diversity. As a result, the variations in different genes could be responsible for the clinical findings of this disease. In previous studies genes encoding Angiotensin-Converting Enzyme (ACE) and IL-4 (Interleukin-4) were found to be associated with rheumatologic and autoimmune diseases. In the present study we hypothesized whether ACE I/D or IL-4 70 bp variable tandem repeats (VNTR) genes are associated with FMF and its clinical findings in Turkish patients. Genomic DNA obtained from 670 persons (339 patients with FMF and 331 healthy controls) was used in the study. Genotypes for an ACE gene I/D polymorphism and IL-4 gene 70 bp VNTR were determined by polymerase chain reaction with specific primers. To our knowledge, this is the first study examining ACE gene I/D polymorphism and IL-4 gene 70 bp VNTR polymorphism in FMF patients. As a result, there was a statistically significant difference between the groups with respect to genotype distribution (p<0.001). According to our results, ACE gene DD genotype was associated with an increased risk in FMF [p<0.001; OR (95%): 7.715 (4.503-13.22)]. When we examined ACE genotype frequencies according to the clinical characteristics, we found a statistically significant association between DD+ID genotype and fever (p=0.04). In addition IL-4 gene P1P1 genotype was associated with FMF (p<0.001). We propose that D allele or DD genotype of ACE gene and P1 allele or P1P1 genotype of IL-4 gene may be important molecular markers for susceptibility of FMF.
家族性地中海热（FMF）的特征是腹膜、滑膜或胸膜反复出现发热和炎症，并伴有疼痛。它是一种常染色体隐性疾病，由MEFV（地中海热）基因突变引起。具有相似基因型的患者表现出表型多样性。因此，不同基因的变异可能是导致该疾病临床表现的原因。在先前的研究中，发现编码血管紧张素转换酶（ACE）和白细胞介素-4（IL-4）的基因与风湿性和自身免疫性疾病有关。在本研究中，我们假设ACE I/D或IL-4 70 bp可变串联重复序列（VNTR）基因是否与土耳其患者的FMF及其临床表现有关。本研究使用了从670人（339例FMF患者和331名健康对照）中获得的基因组DNA。通过使用特异性引物的聚合酶链反应确定ACE基因I/D多态性和IL-4基因70 bp VNTR的基因型。据我们所知，这是第一项研究FMF患者中ACE基因I/D多态性和IL-4基因70 bp VNTR多态性的研究。结果，两组在基因型分布方面存在统计学上的显著差异（p<0.001）。根据我们的结果，ACE基因DD基因型与FMF风险增加相关[p<0.001；OR（95%）：7.715（4.503 - 13.22）]。当我们根据临床特征检查ACE基因型频率时，发现DD + ID基因型与发热之间存在统计学上的显著关联（p = 0.04）。此外，IL-4基因P1P1基因型与FMF相关（p<0.001）。我们提出，ACE基因的D等位基因或DD基因型以及IL-4基因的P1等位基因或P1P1基因型可能是FMF易感性的重要分子标志物。
