A single-nucleotide polymorphism (rs8176070) of lncRNA PART1 may reflect the risk for knee osteoarthritis.
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ABSTRACT:
SUBMITTER: Piskin I
PROVIDER: S-EPMC7343226 | biostudies-literature | 2020 Apr
REPOSITORIES: biostudies-literature
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A single-nucleotide polymorphism (rs8176070) of lncRNA PART1 may reflect the risk for knee osteoarthritis.
Pişkin İlkay İ Akcan Gülben G Fırat Ahmet A Tufan Ahmet Çevik AÇ
European journal of rheumatology 20200401 2
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Project description:AbstractPain is one of the most prominent symptoms of osteoarthritis. However, there is often discordance between the pain experienced by individuals with osteoarthritis and the degree of articular pathology. This suggests that individual differences, including genetic variability in the central processing of nociceptive stimuli, may impact the presentation of osteoarthritis. Here, we show that the single nucleotide polymorphism rs16868943 in the collagen gene COL11A2 is significantly associated with lowered heat pain tolerance on the arm in participants with knee osteoarthritis (P = 1.21 × 10−6, P = 0.0053 after Bonferroni correction, beta = −3.42). A total of 161 knee osteoarthritis participants were included and evaluated for heat, punctate and pressure pain sensitivity of the affected knee and the ipsilateral arm. Each participant was genotyped for 4392 single nucleotide polymorphisms in genes implicated in pain perception, inflammation and mood and tested for association with pain sensitivity. The minor A allele of single nucleotide polymorphism rs16868943 was significantly associated with lower arm heat pain tolerance after correction for age, gender, race, and study site. This single nucleotide polymorphism was also nominally associated with other measures of heat pain sensitivity, including lowered knee heat pain tolerance (P = 1.14 × 10−5, P = 0.05 after Bonferroni correction), lowered arm heat pain threshold (P = 0.0039, uncorrected) and lowered knee heat pain threshold (P = 0.003, uncorrected). Addition of genotypes from 91 participants without knee pain produced a significant interaction between knee osteoarthritis status and the rs16868943 single nucleotide polymorphism in heat pain tolerance (P = 1.71 × 10−5), such that rs16868943 was not associated with heat pain tolerance in participants without knee pain (P = 0.12, beta = 1.3). This is the first study to show genetic association with heat pain tolerance in individuals with osteoarthritis. The association is specific to participants who have already developed knee osteoarthritis, suggesting that the COL11A2 gene, which has previously been associated with familial osteoarthritis, may play a role in pain sensitization after the development of osteoarthritis.
| S-EPMC5562334 | biostudies-literature
Project description:BackgroundOsteoarthritis (OA) is a chronic degenerative disorder probably affected by both genetic and environmental causes. Bone morphogenetic proteins (BMPs) are bone-derived factors that can induce new bone formation. Single-nucleotide polymorphisms (SNPs) of BMP5 gene alters the transcriptional activity of the BMP5 promoter that has been involved in OA susceptibility. This case-control study investigated the association of rs1470527 and rs9382564 SNP of BMP5 gene with susceptibility to knee OA (KOA).Materials and methodsA total of 499 cases with radiographic KOA and 458 age- and sex-matched healthy controls were enrolled. Venous blood samples were obtained from all the cases as well as controls for polymerase chain reaction-restriction fragment length polymorphism.ResultsThe genotype distribution for rs1470527 and rs9382564 SNP was significantly different in cases and controls (P < 0.0001). Within both the SNPs of BMP5 gene, genotype CT and TT were significantly (P < 0.0001) associated with KOA as compared to the CC genotype. T allele of both the studied SNP was significantly associated with KOA (P < 0.0001). The allele frequencies of rs1470527 were 0.56(T) and 0.44(C) in cases and 0.33(T) and 0.67(C) in controls and in rs9382564 were 0.57(C) and 0.43(T) in cases and 0.71(C) and 0.29(T) in controls. Further in relation with clinical severity of OA, we observed signification association of TT genotype with both visual analog scale (P < 0.0001) and Western Ontario and McMaster Universities score (P < 0.05).ConclusionOur results indicate significant association of rs1470527 and rs9382564 polymorphism of BMP5 gene with KOA.
| S-EPMC5525478 | biostudies-literature
Project description:OBJECTIVE:To investigate the association between SNP in the BTNL2 gene region and the susceptibility to osteoarthritis of the knee. METHODS:The blood samples of 103 knee osteoarthritis and 134 healthy subjects were collected. Four SNP in the BTNL2 gene region were selected, whole DNA was extracted using the QIAamp blood DNA purification mini reagent, the BTNL2 gene fragment was amplified and sequenced, and the genotype and corresponding frequency were counted. The results were statistically analyzed. RESULTS:The four SNP (rs41521946, rs28362677, rs28362678, rs28362675) in the BTNL2 gene region were analyzed using a chi-square test (mutation heterozygote, homozygous, and normal homozygote), and the genotypes of the four mutation points were found to be statistically significant (P=0.003, 0.013, 0.005, and 0.045, respectively). Among the four SNP, the first three SNP were in Hardy-Weinberg equilibrium, and a multivariate logistic regression analysis was used to correlate them with knee osteoarthritis (P=0.003, 0.013, 0.005, respectively). rs28362675 was not in Hardy-Weinberg equilibrium but was associated with knee osteoarthritis (P=0.045), which might be smaller samples or an ethnicity differential allelic variation. The P values of the statistical analysis of age and height in the baseline data of both groups were less than 0.05. Considering the possible impact on the results, they were used as covariates in the analysis. The SNP of rs41521946 and rs28362677 showed a significant change in their associations with mutations, and the genotype P values of rs41521946 (AC+AA)/CC and rs2836267 (AG+AA)/GG were 0.002, 0.006, respectively. CONCLUSION:Four SNP (rs41521946, rs28362677, rs28362678, rs28362675) in the BTNL2 gene region were significantly associated with knee osteoarthritis, and the target population might be significantly affected by rs28362675.
| S-EPMC6949757 | biostudies-literature
Project description:ObjectiveOsteoarthritis (OA) is a complex arthritic condition in which the genetic factor plays a major role. One of the candidate genes of is the ADAM12 gene, but no consistency has been reached till now. This study aims to investigate the potential role of four single nucleotide polymorphisms (SNPs) of the ADAM12 gene in susceptibility to knee OA and its progression in Chinese Han population.MethodsThe rs1278279, rs3740199, rs1044122, and rs1871054 polymorphisms were genotyped and compared in a population based cohort consisting of 164 OA subjects and 200 age- and gender-matched controls.ResultsThe SNP rs1871054 was found with increased risk of OA susceptibility in comparing the genotype frequencies between the case and control groups no matter for which model of comparison (allele level, dominant model, recessive model, and extreme genotype model). Additionally, the SNP rs1871054 was found associated with increased OA severity according to the K/L grade.ConclusionIn summary, we have identified that the rs1871054 variant within the ADAM12 gene is a risk factor for increased osteoarthritis susceptibility and severity.
| S-EPMC4312576 | biostudies-literature
Project description:ObjectiveADAM12 polymorphisms may be associated with the risk of knee osteoarthritis (KOA), but currently available evidence remains controversial. We performed this meta-analysis to confirm whether ADAM12 polymorphisms were associated with susceptibility of KOA.MethodsA comprehensive literature search in PubMed, EMBASE, and ISI Web of Science was conducted to identify observational studies assessing the association between ADAM12 polymorphisms and susceptibility of KOA. The strength of association was indicated as odds ratio (OR) and the corresponding 95% confidence interval (95%CI). Four types of genetic model (additive model, dominant model, recessive model, and allele model) were evaluated for each included study. Subgroup analysis by ethnicity was performed.ResultsSeven case-control studies comprising a total of 3512 KOA patients and 5405 healthy controls were included in the meta-analysis. A significant association between rs1871054 and increased KOA risk was found in each genetic model. No significant association was found between KOA and rs3740199, rs1044122, or rs1278279 in any genetic model.ConclusionBased on the findings of our study, there was a modest but statistically significant association between rs1871054 and risk of KOA in Asian population, while other polymorphisms (rs3740199, rs1044122, or rs1278279) in ADAM12 were not associated with KOA in any population.
| S-EPMC5591934 | biostudies-literature
Project description:IntroductionThe role of genetic factors influencing osteoarthritis (OA) susceptibility is well documented and several candidate genes have been identified to be associated with it. Among these genes are Bone Morphogenetic Protein 5 (BMP5) and Smad family member 3 (SMAD3), all involved in Transforming Growth Factor (TGF) signaling pathway. The knee is the commonly affected joint, and knee OA has an especially high prevalence in Asian population.AimTo investigate associations between Single Nucleotide Polymorphisms (SNPs) rs12901499 in SMAD3 and rs921126 in the BMP5 gene with knee OA susceptibility in and around Lucknow, Uttar Pradesh, India.Materials and methodsSNPs rs12901499 in SMAD3 and rs921126 in BMP5 were genotyped in patients with knee OA and age- sex matched OA-free controls from our population. A total of 450 patients with knee OA and 458 controls were enrolled in the study. Venous blood samples were obtained from all cases as well as controls for PCR-RFLP (Polymerase Chain Reaction- Restriction Fragment Length Polymorphism). Data was collected and entered in excel sheets. Statistical analyses of the data were performed using statistical software package SPSS version 16.0. Chi-square, Student's t-test and logistic regression tests were used to analyse the data.ResultsGA and GG genotypes of both SNPs (rs12901499 and rs921126), and variant G, were associated with a significantly increased risk of knee OA. A significantly increased risk of knee OA was associated with the genotype GG and GA of rs12901499 (p < 0.03 and p <0.004 respectively) and rs921126 (p< 0.0001 and p<0.001 respectively) compared with the AA genotype. In addition, those bearing at least one G allele (GG + GA) had a significantly increased risk of knee OA compared with those without the G allele (AA) in rs921126 (p< 0.0001). However, in rs12901499, significant association with the risk of knee OA was not found (p<0.4). On age and gender based stratification, the association between the risk of OA and rs921126 GG mutant compared with AA homozygotes was strong in both gender (adjusted OR= 2.93 for male and 2.25 for female) and in those aged >55 years (adjusted OR= 3.4), similarly in rs12901499, GG mutant compared with AA homozygote was strong in female (adjusted OR= 1.5) and in those aged >55 years (adjusted OR= 1.5).ConclusionThe results showed that both in SMAD3 rs12901499 and BMP5 921126, G allele is significantly associated with knee OA. A to G change and variant G genotype may contribute to knee OA risk in our study population of Lucknow.
| S-EPMC5535387 | biostudies-literature
Project description:IntroductionGenetic factors including the level of expression of the fingerprint of genes involved in the development of bones and cartilage such as GDF-5 or ESR-α or CALM-1 are known to be strong determinants of the osteoarthritis (OA) in Caucasian and Oriental populations. Because of high prevalence of OA in Indian population and availability of limited genetic data, we determined whether similar genetic factors are involved in Indians as well.MethodsA case control study was carried out involving 500 patients of knee OA and equal number of healthy controls. Genotyping analyses in whole blood, mRNA, and protein expressions in peripheral blood lymphocytes (PBLs) were performed using established protocols.ResultsOur results showed a significantly decreased level of mRNA and protein expressions for GDF-5, ESR-α, and CALM-1 genes in PBLs of OA cases when compared to healthy controls. The frequency of variant genotypes of these genes was also increased significantly in cases of OA compared to controls.ConclusionOur results demonstrated that the decrease in expression of GDF-5, ESR-α, and CALM-1 in PBLs and association of polymorphism in these genes may be important in predicting the severity and thereby the progression of OA in Indian population.
| S-EPMC5654253 | biostudies-literature
Project description:Matrix metalloproteinase 1 (MMP-1) degrades cartilage, which may result in osteoarthritis (OA) development. Several studies have explored the association between MMP-1 gene rs1799750 polymorphism and OA in different populations. However, the results are inconsistent. The aim of this case-control study was to investigate the association between MMP-1 gene rs1799750 polymorphism and knee OA in a Chinese population. The present study included 308 cases and 404 controls. Genotyping was performed using standard polymerase chain reaction and restriction fragment length polymorphism. The present study found that 2G2G genotype (2G2G vs 1G1G: OR & 95% CI, 2.28 (1.47-3.53), P<0.001; 2G2G + 1G2G vs 1G1G: OR & 95% CI, 1.61 (1.15-2.24), P=0.005; 2G2G vs 1G2G + 1G1G: OR & 95% CI, 1.84 (1.26-2.68), P=0.002) or 2G allele carriers (2G vs 1G: OR & 95% CI, 1.48 (1.20-1.83), P<0.001) of MMP-1 gene rs1799750 polymorphism increased the risk of OA. In conclusion, this case-control study confirms that MMP-1 gene rs1799750 polymorphism increases the risk of knee OA in Chinese Han population.
| S-EPMC6146290 | biostudies-literature
Project description:AimThis study aimed to determine the genetic association between Growth Differentiation Factor 5 (GDF5) gene (rs143383 T/C) single nucleotide polymorphism (SNP) and primary knee osteoarthritis (OA) in a group of Egyptian patients.Patients and methodsThe study included 47 patients with primary knee OA and 40 apparently healthy control subjects. The disease was assessed using Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score and Health Assessment Questionnaire (HAQ). Radiological assessment was done by Kellgren-Laurence (K/L) grading system. The genetic association of the SNP with primary knee OA was assessed by restriction fragment length polymorphism - polymerase chain reaction (RFLP-PCR).ResultsThe mean total WOMAC index was significantly higher in patients with TT genotype as compared to patients with CC and CT genotypes (P<0.001). Similarly, the HAQ score was significantly higher among patients with TT genotype when compared to patients with CT and CC genotypes (P<0.001). There was a statistically significant association between different GDF5 genotypes and K/L radiological grading of knee OA among the studied patients (P=0.029). No statistically significant association was detected on comparing the frequency distribution of GDF5 alleles and genotypes frequencies of the SNP in patients and healthy controls.ConclusionThere is a possible genetic association between GDF5 (rs143383) SNP and severity of primary knee OA, which might facilitate the detection of patients with high risk for disease progression. The present study did not detect an association between the SNP and development of primary knee OA.
| S-EPMC7045969 | biostudies-literature
Project description:BackgroundSeveral case-control studies have been conducted to clarify the association between the tumor necrosis factor alpha (TNF-α) -G308A polymorphism and risk of osteoarthritis (OA); however, the results are inconsistent. This meta-analysis was performed to clarify this issue using all the available evidence.MethodsEligible articles were retrieved by searching PubMed, Web of science and Google scholar. The strength of the association between the TNF-α -G308A polymorphism and risk of OA was assessed by odds ratios (ORs) with the corresponding 95% confidence interval (CI) for each study.ResultsSeven studies were included in the meta-analysis, which included 983 OA cases and 1355 controls. The pooled analysis based on all included studies showed a significantly increased OA risk in the recessive genetic model analysis (OR = 11.08, 95% CI = 4.75-25.86, p < 0.001) and in the A allele vs. G allele analysis (OR = 2.30, 95% CI = 1.08-4.90). However, there was no statistical difference in the dominant genetic model analysis (OR = 2.45, 95% CI = 0.95-6.27, p = 0.06). Furthermore, we found that OA patients had a higher frequency of the AA genotype (OR = 10.49, 95% CI = 4.47-24.61) and GA genotype (OR = 1.78, 95% CI = 1.03-3.08) compared with the control population.ConclusionOur results suggested that the TNF-α -G308A polymorphism were associated with an increased risk of OA.
| S-EPMC4289255 | biostudies-literature