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Background: This case-control study aims to examine the association between the Interleukin-6 (IL-6) rs12700386 polymorphism and the increased risk of developing osteoarthritis (OA) in the knee in the Chinese Han population., Methods: We extracted DNA from 763 subjects (352 OA patients and 411 healthy controls). The relative expression levels of IL-6 in blood samples of patients with knee OA was determined by quantitative reverse transcription PCR (qRT-PCR) and polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) was used for genotyping the IL-6 gene polymorphism., Results: We found that the IL-6 polymorphism rs12700386 enhanced patient susceptibility to developing knee OA. Based on a subgroup analysis, the risk of developing knee OA was elevated in smokers, drinkers, and subjects ≥55 years old or with BMI ≥ 25 kg/m 2 . The combination of smoking, drinking, and having the rs12700386 genotype led to an increase in the risk of developing knee OA, indicating that an underlying interaction between gene and environment exists. The rs12700386 genotype was found to be correlated with an increase in IL-6 expression. We also found that IL-6 levels were significantly higher in the CC genotype compared to the GG genotype carriers in OA patients., Conclusion: These data suggest that the rs12700386 polymorphism in the IL-6 gene leads to an increase in the risk of knee OA in Chinese Han individuals.

Excessive activation of the Wnt signalling pathway in the articular cartilage is demonstrated to be related to the onset and severity of osteoarthritis (OA). However, few studies have investigated the association between variants in Wnt-pathway-related genes and the risk of OA by searching Pubmed and EMBASE. Totally, 471 knee OA patients and 532 controls were recruited from three hospitals to evaluate the associations of five genetic variants (rs61735963, rs2908004, rs10795550, rs1799986 and rs1127379) with the risk of knee OA. These polymorphisms were genotyped through polymerase chain reaction and Sanger sequencing. Genetic risk scores (GRSs) were calculated to evaluate the combined effect of these genetic variants. No significant association was found between OA risk and polymorphisms (rs61735963, rs10795550 or rs1127379). However, WNT16 rs2908004 polymorphism was correlated with a decreased risk of OA, especially among females, smokers, non-drinkers and individuals with age < 60 years or BMI ≥ 25. This SNP was also associated with Kellgren-Lawrence grade and CRP. Similarly, LRP1 rs1799986 polymorphism decreased the risk of OA among males, smokers, drinkers and individuals with age < 60 years or BMI ≥ 25. TT genotype was more frequent in the group of VAS ≥ 6 versus VAS < 6. A low GRS was positively correlated with a decreased risk of OA. In addition, rs2908004 or rs1799986 polymorphism reduces the expression of WNT16 or LRP1. In conclusion, two SNPs (rs2908004 and rs1799986) are associated with the decreased risk of OA by regulating the Wnt pathway., (© 2019 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

The mTOR signaling pathway has been demonstrated to be related to the development of osteoarthritis (OA) by regulating expression of autophagy regulators. Few studies have shed light on the association of mTOR-pathway-related gene variants with OA risk. Totally 441 OA patients and 533 controls were recruited and their genotypes for mTOR-pathway-related gene variants were determined based on the matrix-assisted laser desorption/ionization time of flight mass spectrometry. Genetic risk scores (GRS) were calculated to evaluate the combined effect of these polymorphisms on OA risk. No significant differences were observed in genotypic and allelic frequencies of AKT rs1130233/REDD1 rs1053639 polymorphisms. However, the mTOR rs1034528 polymorphism was demonstrated to be related to an increased risk of OA, especially among smokers and individuals aged ≥60 years. This single nucleotide polymorphism (SNP) also showed significantly correlation with the Lequesne's index. Similarly, the IRS1 rs1801278 polymorphism increased the risk of OA among smokers, drinkers and individuals aged ≥60 years. A strong positive correlation was found between PTEN rs3830675 polymorphism and OA risk, and this SNP was more frequent in the smokers and drinkers groups. No association was found between IRS1 rs1801278/PTEN rs3830675 polymorphism and OA characteristics. Additionally, there was a strong interaction between genetic factors and lifestyles under the combined models (IRS1 rs1801278/ PTEN rs3830675 polymorphism and smoking/drinking). A high GRS was positively related to an increased risk of OA. In summary, three gene polymorphisms (mTOR [rs1034528], IRS1 [rs1801278] and PTEN [rs3830675]) were found to affect the risk of OA development by regulating the mTOR pathway., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Serum amyloid A (SAA1) is an apolipoprotein that maintains glucose and lipid homeostasis. Its polymorphisms are associated with risks of myocardial infarction and coronary artery disease (CAD). Methods: However, little is known about the associations of these polymorphisms with susceptibility to osteoporosis, which we evaluated in this hospital-based case-control study involving 300 osteoporosis patients and 350 controls. Three single-nucleotide polymorphisms (SNPs) (rs183978373, rs12218, and rs10832915) were genotyped using MALDI TOF MS. Results: There were no differences in the rs183978373 and rs12218 polymorphisms between the osteoporosis group and controls. The SAA1 gene rs10832915 polymorphism increased the risk of osteoporosis in our Chinese population. The genotypes of the rs10832915 polymorphism were not significantly associated with clinical parameters (age, body mass index (BMI), high- and low-density lipoprotein (LDL), total cholesterol (TC), and T-score). Haplotype analysis revealed that the ATT haplotype had a significant correlation with a decreased risk of osteoporosis. Conclusion: In conclusion, the SAA1 rs10832915 polymorphism and its haplotypes are associated with osteoporosis, but this finding should be confirmed in large well-designed studies., (© 2019 The Author(s).)

The autoimmune regulator (AIRE), a transcriptional regulator expressed in medullary thymic epithelial cells, plays an important role in thymocyte education and negative selection. Several citations studying the association between the rs878081 exon polymorphism of the AIRE gene and the risk of rheumatoid arthritis (RA) in different populations have yielded conflicting findings. Thus, this case-control study involving 300 RA cases and 300 controls was aimed to identify whether such association existed in a Chinese Han population from East China. The rs878081 polymorphism of the AIRE gene was genotyped. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using the chi-squared test, genetic model analysis, and stratification analysis. Genetic model analysis showed significant correlations between the TT genotype and the risk of RA (OR: 1.89, 95%CI: 1.03-3.47 in TT vs CC; OR: 1.84, 95%CI: 1.02-3.31 in TT vs CC+TC). Stratification analyses of sex, age, smoking, and alcoholism suggested that the rs878081 polymorphism of the AIRE gene increased RA risk among non-smokers. In conclusion, rs878081 polymorphism of AIRE gene increases the risk of RA in a Chinese Han population.

Accumulating evidences suggested that tumor necrosis factor alpha inducible protein 3 (TNFAIP3) gene rs10499194, rs13207033 polymorphisms may be associated with the risk of rheumatoid arthritis (RA). However, these studies yielded contradictory findings. To clarify convincing associations, we conducted a comprehensive meta-analysis by searching in PubMed, Embase, and the China Knowledge Resource Integrated Database. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by using fixed-effect or random-effect models. A total of 13 case-control studies for rs10499194 polymorphism and 6 studies for rs13207033 polymorphism were included. Our data indicated that TNFAIP3 gene rs10499194, rs13207033 polymorphisms were associated with the decreased risk of RA. Stratification analyses of ethnicity indicated rs10499194, rs13207033 polymorphisms decreased the risk of RA among Caucasian populations, but not among Asian populations. In conclusion, this meta-analysis indicates that TNFAIP3 gene rs10499194, rs13207033 polymorphisms decrease the risk of RA, especially among Caucasian populations.

To investigate the roles of the plasma vascular endothelial growth factor (VEGF) level and VEGF gene polymorphisms in ankylosing spondylitis (AS) susceptibility. The plasma VEGF level was measured using an enzyme-linked immunosorbent assay. The VEGF rs2010963 G/C gene polymorphism was analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Our data indicated that the average plasma VEGF concentration in the AS patients was markedly higher than in the controls. Stratification analysis indicated a significant correlation between an elevated plasma VEGF level in AS patients and sex, but not age, HLA-B27, C-reactive protein (CRP), or grade of the sacroiliac joint. We also found that VEGF rs2010963 G/C was associated with a decreased risk of AS. Significant differences were found between the VEGF rs2010963 G/C genotypes and elevated plasma level in AS patients when compared with the controls. However, we did not find a significant association between the plasma VEGF level and different rs2010963 G/C genotypes in the AS patients or controls. To sum up, serum VEGF levels are significantly associated with the inflammatory process of AS. This study suggests that VEGF is involved in the immunological or inflammatory process of AS., (Copyright © 2016 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.)

Introduction: The aim of the present study was to examine the association between polymorphisms of interleukin 12 (IL-12) and rheumatoid arthritis (RA) associated biomarkers in a Chinese population., Materials and Methods: We studied IL-12A rs2243115 T/G and IL-12B rs3212227 A/C polymorphisms in 615 RA patients and 839 controls in a Chinese population. Genotyping was done by a custom-by-design 48-Plex SNPscan™ Kit. The plasma level of IL-12 was measured by an enzyme-linked immune-sorbent assay in 90 RA patients and 90 controls. Clinical data with other potential diagnostic value were provided by the physicians., Results: A significantly increased risk for RA associated with the IL-12A rs2243115 GG (GG versus TT: OR=4.81, 95% CI 1.33-17.36, P=0.017; and GG versus TG+TT: OR=4.55, 95% CI 1.27-16.36, P=0.020) genotype was evident among rheumatoid factor (RF) negative patients, and with the IL-12B rs3212227 AC (AC versus AA) and AC+CC (AC+CC versus AA) genotypes were evident among older patients (OR=1.48, 95% CI 1.06-2.06, P=0.020), RF positive patients (OR=1.35, 95% CI 1.04-1.75, P=0.026) and anti-cyclic citrullinated peptide antibodies (ACPA) negative patients (OR=1.53, 95% CI 1.11-2.10, P=0.009). The plasma level of IL-12 was significantly higher in RA patients (P<0.001). IL-12 plasma level of IL-12A rs2243115 TT (P<0.001) and IL-12B rs3212227 C allele (P<0.001) were significantly higher in RA patients than controls respectively. The plasma level of IL-12 of RF positive RA patients was significantly higher than RF negative patients (P=0.008), especially in rs3212227 AC patients (P=0.01)., Conclusions: These findings suggested that the functional single nucleotide polymorphism (SNP) IL-12A rs2243115 GG genotype may increase the risk of RA in RF negative patients, and the IL-12B rs3212227 AC and AC+CC genotypes are associated with RA risk in older patients, RF positive patients and ACPA negative patients. The IL-12A rs2243115 T/G and IL-12B rs3212227 A/C allele might also impact the inflammatory reaction of IL-12 in patients with RA., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Prosthetic joint infection (PJI) is the most common cause of total joint arthroplasty failure and revision surgery. Genetic polymorphisms could be determinant factors for PJI., Methods: We performed a systematic research of Medline, Pubmed, Embase, Cochrane Library, and Google Scholar, and identified 11 studies with 34 kinds of gene polymorphisms, were included in the synthesis., Results: Our data suggest that the C allele and genotype C/C for MBL-550 SNP, genotype A/A for MBL-54 SNP and G allele for MBL-221 SNP increase the risk of PJI, while G allele and genotype G/G for MBL-550 SNP decrease the risk of PJI in Caucasian populations. Several other genes reported by single-center studies also contribute to the genetic susceptibility to septic PJI. No definitive conclusions could be achieved due to the small amount of data in the included studies., Conclusion: Several genes contribute to the genetic susceptibility to PJI following total joint arthroplasty. Further studies will enhance the understanding of PJI, and may inform and direct early interventions., (Copyright © 2015 Elsevier B.V. All rights reserved.)