RESUMO
To investigate associations of the Fas and FasL genes polymorphisms with rheumatoid arthritis (RA). One hundred patients with RA and age-, sex- and ethnically matched 101 controls were included. Four polymorphisms of Fas (-670 A>G rs1800682, -1377 G>A rs2234767) and FasL (IVS2nt-124 A>G rs5030772, -844 T>C rs763110) genes were typed from genomic DNA. Genotype distributions and allelic frequencies were compared between patients and control subjects. After the history and clinical examination of patients with RA, in terms of pain, fatigue and general health status were evaluated by visual analogue scale. Thereafter, erythrocyte sedimentation rate, C-reactive protein, blood count and rheumatoid factor levels were measured. The Disease Activity Score-28, Health Assessment Questionnaire and modified Sharp score were used to evaluate the disease activity, functional disability and radiological damage, and their relationships with the Fas and FasL gene polymorphisms were investigated. In patients with RA, CT and TT genotypes of FasL-844, polymorphism were twofold and 4.8-fold higher, and AA genotype of FasL IVS2nt-124 polymorphism was 3.4-fold higher than the control group (respectively, p = 0.05, p = 0.002, p = 0.039). T allele of FasL-844 polymorphism was more frequent in patients than controls (respectively, 52.5 vs. 41.4 %, p = 0.027). Any association was not detected between Fas (-670 A>G, -1377 G>A) and FasL (-844 T>C, IVS2nt-124 A>G) gene polymorphisms with the disease activity scores, functional disability and radiological damage. However, the Fas-670 A>G polymorphism was associated with drug therapy (p = 0.049). The distribution of GG genotype was higher compared to GA or AA genotypes in patients using triple disease-modifying antirheumatic drug therapy (71.4, 14.3 and 14.3 %, respectively). These findings suggest that the -844 T>C and IVS2nt-124 A>G polymorphisms in the FasL gene related with apoptosis may increase genetic susceptibility to RA in a Turkish population. In addition, the Fas-670 A>G gene polymorphism may be associated with disease progression. There is a need for further studies to clarify the genetic role of apoptosis in RA.
Assuntos
Artrite Reumatoide/genética , Proteína Ligante Fas/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Receptor fas/genética , Adulto , Idoso , Alelos , Apoptose/genética , Estudos de Casos e Controles , Progressão da Doença , Fadiga/genética , Feminino , Frequência do Gene , Estudos de Associação Genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Dor/genética , Índice de Gravidade de Doença , Turquia , Escala Visual AnalógicaRESUMO
To investigate the associations between Fas and FasL gene polymorphisms and susceptibility to knee osteoarthritis. Genomic DNA was obtained from 146 patients with knee osteoarthritis and 102 healthy controls. Genotype distributions and allelic frequencies of four polymorphisms of Fas (-670 G>A rs1800682, -1377 G>A rs2234767) and FasL (IVS2nt-124 A>G rs5030772, -844 T>C rs763110) genes were compared between the groups. Thereafter, this association was investigated between patients and controls of the same sex. There were significant differences between patients with knee osteoarthritis and controls regarding the genotype distributions and allelic frequencies of Fas-1377 G>A polymorphism (P = 0.0001 and P = 0.005, respectively). The Fas-1377 GG genotype and G allele were significantly more frequent in patients with knee osteoarthritis than in controls. Genotype distributions and allelic frequencies of Fas-670 G>A, FasL-844 T>C, and FasL IVS2nt-124 A>G polymorphisms did not differ between the groups (P > 0.05). However, there were no significant differences between patients and controls of the same sex (P > 0.05). These findings suggest that the Fas-1377 G>A polymorphism in the Fas gene related with apoptosis may contribute to susceptibility to knee osteoarthritis in the Turkish population. There is a need for further studies to evaluate the role of apoptosis in large cohorts.
Assuntos
Proteína Ligante Fas/genética , Predisposição Genética para Doença , Osteoartrite do Joelho/genética , Receptor fas/genética , Idoso , Alelos , Feminino , Frequência do Gene , Estudos de Associação Genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Fatores de Risco , TurquiaRESUMO
The aim of this study was to investigate whether functional polymorphisms in the promoter of matrix metalloproteinase-1 (MMP-1), MMP-2 and MMP-9 genes were associated with susceptibility to knee osteoarthritis in the Turkish population. The MMP-1 -1,607 1G/2G (rs1799750), MMP-2 -1,306 C/T (rs243865), and MMP-9 -1,562 C/T (rs3918242) polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism assay in 157 patients diagnosed with knee osteoarthritis based on the criteria of American College of Rheumatology and in 84 controls in Mersin, Turkey. Genotype distributions and allele frequencies of MMP-1, MMP-2, and MMP-9 gene polymorphisms were compared between the patients and controls. There were significant differences between the groups regarding the genotype distribution of MMP-1 polymorphism (P = 0.001). The frequencies of 1G/1G and 1G/2G genotypes were significantly higher in the knee osteoarthritis than in the controls (P = 0.002, and P = 0.006, respectively). In addition, 1G allele frequency of MMP-1 gene was higher in the patients than in the control group (P = 0.0001). The genotype distributions and allele frequencies of MMP-2 and MMP-9 gene polymorphisms did not differ between the osteoarthritis and the control groups (P > 0.05). These findings suggest that the -1,607 1G/2G polymorphism in the MMP-1 gene may contribute to susceptibility to knee osteoarthritis in the Turkish population.
Assuntos
Predisposição Genética para Doença , Metaloproteinase 1 da Matriz/genética , Osteoartrite do Joelho/genética , Polimorfismo Genético , Idoso , Alelos , Estudos de Casos e Controles , Intervalos de Confiança , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Regiões Promotoras Genéticas , TurquiaRESUMO
PURPOSE: To examine whether polymorphisms of the interleukin 1 receptor antagonist (IL1RN), interleukin 1 alpha (IL1A) and interleukin 1 beta (IL1B) genes are markers of genetic susceptibility to knee osteoarthritis in Turkish patients. METHODS: One hundred and seven patients with knee osteoarthritis and 67 controls were studied. Three polymorphisms of IL1A, IL1B, and IL1RN genes were typed from genomic DNA. Allelic frequencies were compared between patients and control subjects. RESULTS: No significant differences were observed in genotype and allele frequencies of the IL1RN VNTR, IL1A+4845, IL1B+3953 genes polymorphisms between patients and controls. Furthermore, we did not detect any association genotypes of the polymorphisms with the clinical, radiological, and laboratory profiles of patients. CONCLUSIONS: The present study suggest that the IL1RN VNTR, IL1A+4845, IL1B+3953 genes polymorphisms are not genetic markers of susceptibility to knee osteoarthritis in Turkish patients, and are unrelated to the clinical, radiological, and laboratory characteristics of knee osteoarthritis.
