Association of ADAMTS12 polymorphisms with rheumatoid arthritis (original) (raw)
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Arthritis, 2013
Objectives. To investigate associations of selected single-nucleotide polymorphisms (SNPs) in ADAM12 gene with radiographic knee osteoarthritis (rKOA) in Estonian population. Methods. The rs3740199, rs1871054, rs1278279, and rs1044122 SNPs in ADAM12 gene were genotyped in 438 subjects (303 women) from population-based cohort, aged 32 to 57 (mean 45.4). The rKOA features were evaluated in the tibiofemoral joint (TFJ) and patellofemoral joint. Results. The early rKOA was found in 51.4% of investigated subjects (72% women) and 12.3% of participants (63% women) had advanced stage of diseases. The A allele of synonymous SNP rs1044122 was associated with early rKOA in TFJ, predominantly with the presence of osteophytes in females (OR 1.57; 95% CI 1.08-2.29, = 0.018). The C allele of intron polymorphism rs1871054 carried risk for advanced rKOA, mostly to osteophyte formation in TFJ in males (OR 3.03; 95% CI 1.11-7.53, = 0.018). Also the CCAA haplotype of ADAM12 was associated with osteophytosis, again mostly in TFJ in males (= 0.014). For rs3740199 and rs1278279, no statistically significant associations were observed. Conclusion. ADAM12 gene variants are related to rKOA risk during the early and late stages of diseases. The genetic risk seems to be predominantly associated with the appearance of osteophytes-a marker of bone remodelling and neochondrogenesis.
Egyptian Rheumatology and Rehabilitation, 2022
Background Primary osteoarthritis is considered one of the most common and the most studied musculoskeletal disorder. Nevertheless, the risk factors remain unclear. A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) 14 (ADAMTS14) gene is involved in the cleavage of amino-terminal propeptides from type II procollagen, a necessary step in the formation of collagen fibers. The abnormal metabolism of collagen fibers type II leads to a decreased mechanical strength of joint cartilage which is one of the most important contributing factors to joint osteoarthritis. We aimed at investigating the association between primary osteoarthritis and ADAMTS14 gene rs4747096 single nucleotide polymorphism in a sample of Egyptian patients and analyzing the relationship between this genetic polymorphism with the severity of osteoarthritis. Sixty-five Egyptian patients who fulfilled the American College of Rheumatology criteria for primary knee osteoarthritis were compared with thir...
Arthritis, 2013
Objectives. To investigate associations of selected single-nucleotide polymorphisms (SNPs) in ADAM12 gene with radiographic knee osteoarthritis (rKOA) in Estonian population. Methods. The rs3740199, rs1871054, rs1278279, and rs1044122 SNPs in ADAM12 gene were genotyped in 438 subjects (303 women) from population-based cohort, aged 32 to 57 (mean 45.4). The rKOA features were evaluated in the tibiofemoral joint (TFJ) and patellofemoral joint. Results. The early rKOA was found in 51.4% of investigated subjects (72% women) and 12.3% of participants (63% women) had advanced stage of diseases. The A allele of synonymous SNP rs1044122 was associated with early rKOA in TFJ, predominantly with the presence of osteophytes in females (OR 1.57; 95% CI 1.08-2.29, = 0.018). The C allele of intron polymorphism rs1871054 carried risk for advanced rKOA, mostly to osteophyte formation in TFJ in males (OR 3.03; 95% CI 1.11-7.53, = 0.018). Also the CCAA haplotype of ADAM12 was associated with osteophytosis, again mostly in TFJ in males ( = 0.014). For rs3740199 and rs1278279, no statistically significant associations were observed. Conclusion. ADAM12 gene variants are related to rKOA risk during the early and late stages of diseases. The genetic risk seems to be predominantly associated with the appearance of osteophytes-a marker of bone remodelling and neochondrogenesis.
Genetic Case-Control Study for Eight Polymorphisms Associated with Rheumatoid Arthritis
PLOS ONE, 2015
Rheumatoid arthritis (RA) is an autoimmune disease which has a significant socio-economic impact. The aim of the current study was to investigate eight candidate RA susceptibility loci to identify the associated variants in Egyptian population. Eight single nucleotide polymorphisms (SNPs) (MTHFR-C677T and A1298C, TGFβ1 T869C, TNFB A252G, and VDR-ApaI, BsmI, FokI, and TaqI) were tested by genotyping patients with RA (n = 105) and unrelated controls (n = 80). Associations were tested using multiplicative, dominant, recessive, and co-dominant models. Also, the linkage disequilibrium (LD) between the VDR SNPs was measured to detect any indirect association. By comparing RA patients with controls (TNFB, BsmI, and TaqI), SNPs were associated with RA using all models. MTHFR C677T was associated with RA using all models except the recessive model. TGFβ1 and MTHFR A1298C were associated with RA using the dominant and the co-dominant models. The recessive model represented the association for ApaI variant. There were no significant differences for FokI and the presence of RA disease by the used models examination. For LD results, There was a high D 0 value between BsmI and FokI (D 0 = 0.91), but the r 2 value between them was poor. All the studied SNPs may contribute to the susceptibility of RA disease in Egyptian population except for FokI SNP.
Updates and perspectives on the genetic markers in Rheumatoid Arthritis
Zenodo (CERN European Organization for Nuclear Research), 2022
The research was carried out on a representative group of patients diagnosed with rheumatoid arthritis (RA). We studied the distribution of patients by sex, age group, and disease stage, and we also tried to identify a genetic marker. In this sense, the blood groups of all RA patients were determined. In the study group, the frequency of patients with blood group B was much increased (47%), compared to the frequency of patients with blood group B in the control group (12%). Calculating the relative risk Rr for the disease, of the patients with blood group B, we found that it was 6.5, which indicated a positive association between RA and the blood group B marker. As a result, individuals belonging to blood group B are much more susceptible to RA compared to those who belong to other blood groups. Another genetic aspect of the research was the familial genetic study of RA. Using the family investigation as a method of investigation, we found that the incidence of family cases of RA in the studied group was 13%. RA, being a condition with the polygenic hereditary transmission, it is difficult to calculate the risk of recurrence, however, we found that, in affected families, the genes with "risk" for RA are much more frequent than in families where they were not observed, in the direct or collateral ancestry, other subjects diagnosed with RA. These observations are of particular importance in the prophylaxis of this condition.
Roles of Genes in the Susceptibility to and Severity of Rheumatoid Arthritis - A Review
Journal of Medicine, 2012
Rheumatoid arthritis is the most common cause of inflammatory polyarthritis in adults. 1 Many studies suggest that RA involves a combination of genetic factors, including genetic markers as well as familial transmission and environmental factors. The most compelling evidence for a genetic component is in monozygotic twins, in whom the concordance rate is 12% to 15% when one twin is affected compared with 1% for the general population. The risk for a fraternal twin of a patient with RA also is high (about 2% to 5%), but this is not more than the rate for other first-degree relatives. 2,3,4,5 Although the immunogenetics is, at best, incompletely understood, one of the best-studied and perhaps most influential genetic risk factors is the class II MHC haplotype of an individual.
Egyptian Journal of Medical Human Genetics, 2022
Background: Rheumatoid arthritis (RA) is an autoimmune disease in which the immune system attacks the tissues of the joints by mistake. Different factors-either genetic or environmental-affect the development of the RA disease in patients. A lot of studies aimed to examine the genetic associations with this disease in different populations. This research aspires to perform a genetic association study between six single-nucleotide polymorphisms (SNPs) and RA disease in the Egyptian population with 49 controls and 52 patients. The SNPs that are included in this study are MIR146A rs2910164 (C:G), MIR499/MIR499A rs3746444 (T:C), MTMR3 rs12537(C:T), MIR155HG rs767649 (A:T), IRAK1 rs3027898 (A:C) and PADI4 rs1748033 (C:T). Methods: Real-time PCR with TaqMan allelic discrimination assay were both used to perform the genotyping. The Odds ratio models with 95% confidence interval were used to test the associations. The used models are multiplicative, recessive, dominant and co-dominant. The demonstrated results indicated that rs2910164 and rs12537 were associated with RA, while rs3746444 showed no association in all the tested models. The remaining SNPs were excluded as they didn't pass the Hardy-Weinberg equilibrium test. The MIR146A and MTMR3 polymorphisms showed susceptibility to RA. Moreover, MIR499/MIR499A had no role in the disease. 1. MIR146A (C allele) had a protective role in rheumatoid arthritis association. MTMR3 was associated with rheumatoid arthritis using the dominant, Co-dominant heterozygote and recessive models. MIR499/ MIR499A had no association with rheumatoid arthritis.