RESUMEN
AIM OF THE STUDY: The present case control study was conducted to assess the association of LTA 252 A>G, TNF-α 308 G>A, and TNF-α 1031 T>C gene polymorphisms with rheumatoid arthritis (RA), and their involvement in disease activity and severity. MATERIAL AND METHODS: A total of 70 Egyptians, including 35 RA patients and 35 healthy control individuals, were included in the study. The RA patients comprised 34 females and one male. Cases with RA were diagnosed by a rheumatologist and fulfilled the 2010 ACR/EULAR criteria. Modified disease activity score (DAS28) was used to assess disease activity. Van Der Heijde-modified Sharp score (vdHSS) was used to assess radiological changes for assessment of disease severity. PCR-RFLP was used to detect the association of LTA 252 A>G, TNF-α 308 G>A, and TNF-α 1031 T>C gene polymorphisms with RA. RESULTS: TNF-α 308 G allele and TNF-α 308 GG genotype were significantly higher in RA patients compared to healthy control subjects (p = 0.04 and p = 0.001, respectively). TNF-α 308 G allele and GG genotype were significantly higher in the RA non-remission group compared to the remission group (p = 0.008, p < 0.001). Patients with the TNF-α 308 AG genotype had higher mean of Sharp score compared to the patients with the GG and AA genotypes (p = 0.007). There was no significant association between LTA 252 A>G and TNF-α 1031 T>C gene polymorphisms and RA. CONCLUSIONS: Our results suggest that TNF-α 308 G/A gene polymorphism is genetically associated with RA and involved in disease activity and severity in Egyptian patients.
RESUMEN
OBJECTIVES: Methyl-CpG-binding protein 2 (MECP2) and interleukin-1 receptor-associated kinase (IRAK1) are encoded by adjacent X-linked genes and recognized for their role in regulation of inflammation. The present case control study was conducted to detect the genetic association between MECP2 (rs1734791) and IRAK1 (rs1059703) single nucleotide polymorphisms (SNPs) and susceptibility to systemic lupus erythematosus (SLE), and the possible association of these SNPs and severity of SLE. MATERIAL AND METHODS: Fifty patients with SLE and 100 healthy controls were included in this study. Systemic Lupus International Collaborating Clinics (SLICC) criteria were used to classify SLE patients and the activity of the disease was assessed by SLEDAI score. Disease severity was assessed by the SLICC damage index (SLICC DI). Genetic association of both SNPs with SLE was assessed by Taq Man allelic discrimination technique. RESULTS: Analyses of MECP2 (rs1734791) SNP genotypes revealed that homozygous TT genotype was significantly higher in the control group than SLE patients (p < 0.001, odds ratio [OR] = 0.120). Frequency of allele (A) was significantly higher in SLE patients, (p < 0.001, OR = 0.334). SLE patients had significantly higher frequency of the homozygous AA and heterozygous AG genotype of IRAK1 (rs1059703) SNP in comparison to healthy controls (p = 0.0029, OR = 4.17 and 6.30 respectively). T+G and T+A of rs1734791 and rs1059703 SNPs are protective haplotypes (OR = 0.47 and 0.3, p = 0.0046 and < 0.012 respectively). No significant association between either SNP and disease activity or severity was found. CONCLUSIONS: There is a possible genetic association between both rs1734791 and rs1059703 SNPs and susceptibility to SLE, while no significant association between either SNP and disease activity or severity was detected.
RESUMEN
Rheumatoid arthritis (RA) is a chronic auto-inflammatory disease of connective tissue with progressive joint damage and systemic disorders. RA is considered a multifactorial disease triggered by a genetic predisposition and environmental factors. Polymorphisms have been identified in the Xq28 locus as risk loci for RA. The aim of study was to assess the association between two polymorphisms in the Xq28 region containing Transmembrane Protein 187 (TMEM187) gene (rs13397) and interleukin1 receptor associated kinase (IRAK1) gene (rs1059703) with the disease susceptibility and activity in Egyptian RA patients. This study was conducted on 100 RA patients and 100 age and sex matched normal controls, together were recruited from the Rheumatology Department, Beni-Suef University Hospital. We detected TMEM187 (rs13397) and IRAK1 (rs1059703) gene polymorphisms using the real time PCR TaqMan allelic discrimination assays. We found that the frequency of the major genotypes (GG) of TMEM 187 gene was higher in RA group (54%) compared to controls (50%); while the minor genotypes (AA) was higher in the control group (22%) compared to the diseased one (18%), but such differences did not reach statistical significance (p=0.599). Regarding the IRAK1 gene, we revealed that the frequency of the major genotypes (AA) of the rs1059703 was slightly higher in RA group (48%) compared to controls (46%); while the minor genotypes (GG) was the same in both groups (26%). However, there was higher incidence of minor genotype in the TMEM187 and IRAK1 genes in males; with a statistical significance (p=0.004 and 0.015, respectively). We concluded that the major allele G of TMEM187(rs 13397) could be considered as a risk genetic allele for RA in Egyptian populations.