Two Single-Nucleotide Polymorphisms in ADAM12 Gene Are Associated with Early and Late Radiographic Knee Osteoarthritis in Estonian Population (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.
Osteoarthritis and Cartilage, 2009
Objective: One of the recognized candidate genes of osteoarthritis (OA) is the ADAM metallopeptidase domain 12 (meltrin alpha) gene. We investigated the potential role of two single nucleotide polymorphisms (SNP) of the ADAM12 gene in susceptibility to radiographic knee OA and its progression in an Estonian cohort. Methods: The rs3740199 and rs1871054 polymorphisms were genotyped according to restriction fragment polymorphism in a populationbased cohort consisting of 189 subjects selected from the age group 32e55 years. The radiological features of OA were measured in the tibio-and patellofemoral joints (PFJ). The X-ray investigation was repeated 3 years later for estimation of OA progression. Results: We found statistically significant association between rs3740199 polymorphism and patellofemoral OA in male patients (P ¼ 0.014), genetic risk was mostly related to CC homozygosity. The same SNP also affected the presence of advanced grade (II þ III) osteophytes in the whole group (P ¼ 0.042) and the occurrence of osteophytes on the patellar margins in the PFJ (P ¼ 0.046). In OA progression the most significant association was found between joint space narrowing of the tibiofemoral joint and rs3740199 SNP in women (P ¼ 0.018). The rs1871054 polymorphism was not related to OA susceptibility or to progression traits. In our study the haplotype GC (rs3740199/ rs1871054) was associated with reduced risk for development of osteophytes in the PFJ (P ¼ 0.041). Conclusions: We conclude that rs3740199 polymorphism may affect occurrence of knee OA and its progression. We also hypothesize that the genetic contribution of ADAM12 to OA is remarkably gender-dependent and anatomical site-specific.
Rheumatology International, 2011
ADAM12 (A disintegrin and metalloprotease) is one of the candidate genes demonstrating susceptibility to osteoarthritis. The purpose of this study was to investigate the relationship between ADAM12-S protein and radiographic knee osteoarthritis (KOA) and its correlation to several bone and cartilage biomarkers. The ADAM12-S protein was measured in 276 subjects (60% women, aged 32-60 years), including 181 individuals with and 95 without radiographic KOA features. The radiographs were obtained from both tibiofemoral (TF) and patellofemoral (PF) joints. The serum levels of ADAM12-S protein were measured by DELFIA1/AutoDELFIA research kit. The ADAM12-S protein was found in detectable ranges in 43 subjects (16 men), without statistical diVerence between the two genders. In the whole group, the ADAM12-S was related to radiographic KOA grades in TF (P = 0.004) as well in PF joint (P = 0.003). We also found a correlation between ADAM12-S protein and osteophytes in TF and/or PF joints (P = 0.003). No correlations were found between serum levels of S-CTx-I (C-terminal cross-linked telopeptides of type I collagen) or S-PINP (type I procollagen N-terminal propeptide) and ADAM12-S. Similarly, in the whole group, the ADAM12-S protein was not correlated with U-CTx-II (urinary C-telopeptide fragments of type II collagen); however, in the female group, trend to positive correlation between the investigated biomarkers (P = 0.019) was observed. The ADAM12-S protein could be elevated in some KOA cases, and this elevation correlates with the grades of the disease, mostly owning to development of osteophytes. This Wnding suggests the possible involvement of the ADAM12-S protein in the pathogenesis of KOA.
Joint Diseases and Related Surgery
Objectives: The aim of this study was to investigate the relationship between MMP13 rs3819089, ADAM12 rs3740199 and rs1871054, and ADAMTS14 rs4747096 genotypes in patients with radiologically diagnosed knee osteoarthritis (OA). Patients and methods: A total of 300 patients (68 males, 232 females; mean age: 61.6 years; range, 25 to 89 years) who were admitted to the orthopedics and traumatology clinic and diagnosed with knee OA according to the 2000 American College of Rheumatology (ACR) criteria between October 2018 and March 2019 were prospectively analyzed. Patients with Grades III-IV OA according to the Kellgren- Lawrence (K-L) grading system were included in the patient group (n=150) and those without radiological features of knee OA (K-L Grades I-II) were included in the control group (n=150) voluntarily. The presence of single nucleotide polymorphisms (SNPs) in the targeted genes in both groups was assessed by real-time polymerase chain reaction in the peripheral blood sample....
ADAMTS14 gene polymorphism associated with knee osteoarthritis in Thai women
Genetics and Molecular Research, 2013
Osteoarthritis (OA) is the most prevalent form of arthritis in the elderly. This disease is characterized by breakdown and loss of articular cartilage due to genetic, mechanical and environmental factors. Although the pathophysiology of OA is not completely known, several candidate genes have been reported to be associated with OA susceptibility. We assessed the association between genetic variation in the ADAMTS14 region and knee osteoarthritis susceptibility in the Thai population. The rs4747096 SNP was genotyped by PCR-RFLP on genomic DNA extracted from peripheral blood of 108 OA patients and 119 controls. The PCR product (196 bp) was digested with BspEI. A sample with the GG genotype showed two band sizes of 158 and 38 bp, while a sample with the AA genotype showed a single band size of 196 bp. Heterozygotes with the AG genotype showed all three corresponding bands. Genotype distributions, ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 12 (4): 5301-5309 (2013) T. Poonpet et al. allele frequencies and model of inheritance in patients and controls were compared. In females, the frequency of the AA genotype and the A allele were significantly higher in knee OA patients than in controls [odds ratio (OR) = 2.79, 95% confidence interval (CI) = 1.05-7.59 and OR = 1.58, 95%CI = 1.00-2.45, respectively]. Moreover, genotypic AA and AG were associated with significantly increased risk for knee OA when compared to GG (OR = 2.72, 95%CI = 1.10-6.87). No significant associations were observed in males. In conclusion, the nsSNP rs4747096 in ADAMTS14 was associated with knee OA in female Thai patients; therefore, the role of ADAMTS14 in OA seems to be gender-dependent.
Genetics and Molecular Research, 2016
Considering the functions of aggrecanase-1 (ADAMTS4) and-2 (ADAMTS5), which are thought to be the two major enzymes responsible for the destruction of aggrecans in arthritic diseases, we investigated whether important polymorphisms in the ADAMTS4 and ADAMTS5 genes affect osteoarthritis (OA) susceptibility. Our study took place in Mugla, Turkey. Ninety-five cases were recruited following OA diagnosis (72 women and 23 men), and 80 individuals without any symptoms or radiographic signs of OA (56 women and 24 men) were chosen as healthy controls. After obtaining DNA from 2 U. Canbek et al. Genetics and Molecular Research 15 (3): gmr.15038264 patients and control subjects, ADAMTS4 and ADAMTS5 genotypes were determined using the ABI Prism StepOnePlus Real-Time system. In addition, we categorized patients based on OA grade. There were no significant differences in the genotype distributions of the four polymorphisms between the groups (P > 0.05). Moreover, ADAMTS4 and ADAMTS5 allele frequencies did not differ between OA and control participants (P > 0.05). These findings suggest that the ADAMTS4 (rs4233367 and rs11807350) and ADAMTS5 (rs226794 and rs2830585) variants examined may not contribute to susceptibility to knee OA in the Turkish population. Other gene polymorphisms should be assessed in order to explain variations in OA susceptibility.
International Journal of Rheumatic Diseases, 2016
Objective: The aim of this study is to determine the role of cytosine-adenine (CA) micro-satellite repeat sequence of ADAMTS9 gene on the development and progression of osteoarthritis (OA). Methods: A total of 110 participants, including those with primary knee OA and healthy controls were enrolled in the study. Patients were stratified into two groups using the Kellgren-Lawrence staging (K-L staging) as group 1 for controls and mild OA and group 2 for moderate and severe OA. Genetic analyses were performed to determine the CA repeat length in ADAMTS9 gene. Results: Twenty CA repeats were found to be statistically significant for differentiating groups 1 and 2 (P = 0.020). Age was the most significant risk factor involved, followed by ≥ 20 CA repeats and body mass index (P < 0.05). CA repeat length of ≥ 20 showed a 6.1-fold increase in probability for having OA at stage 3 or 4 compared to those of CA repeat length of < 20 (P = 0.004). In conclusion, the CA repeat length of ≥ 20 has a six-fold increase in probability for having severe OA. Conclusion: ADAMTS9 gene CA repeat polymorphism may be used to determine the prognosis for OA radiologic progression. Being the first in the literature reporting the CA repeat in the promotor region of ADAMTS9 gene in patients with OA, our study could be highlighted further in future research with larger sample size.
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...
Association of ADAMTS12 polymorphisms with rheumatoid arthritis
Molecular Medicine Reports, 2012
a disintegrin and metalloproteinase (ADAM) with thrombospondin type 1 motif 12 (ADAMTS12) is a degradative enzyme that interacts with the degradable fragments of cartilage oligomeric matrix protein, which is a prominent non-collagenous matrix component in articular cartilage.