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SMAD3 gene rs12901499 polymorphism increased the risk of osteoarthritis.

ABSTRACT: A growing body of evidence suggested that smad family member 3 gene rs12901499 polymorphism was associated with the risk of osteoarthritis. However, the results of previous studies were conflicting. In the present study, we assessed whether smad family member 3 gene rs12901499 polymorphism was associated with the risk of osteoarthritis by the meta-analysis. We searched in the databases of PubMed, Embase, and CNKI. Pooled odds ratios and 95% confidence intervals were calculated. Seven papers involving 11 studies (5344 cases and 9080 controls) analyzed the association between smad family member 3 gene rs12901499 polymorphism and osteoarthritis risk. This meta-analysis confirmed that smad family member 3 gene rs12901499 polymorphism increased the risk of osteoarthritis. Stratification analysis of ethnicity found that rs12901499 polymorphism increased the risk of osteoarthritis among both Asians and Caucasians [G vs A: Asians, OR and 95%CI, 1.34(1.07, 1.69), P=0.012; Caucasians, OR and 95%CI, 1.21(1.13, 1.29), P<0.001]. In addition, subgroup analysis by type of osteoarthritis revealed that smad family member 3 gene rs12901499 polymorphism was correlated with the increased risk of hip osteoarthritis, but not associated with knee osteoarthritis. Sensitivity analysis did not draw different findings. In conclusion, this meta-analysis indicates that smad family member 3 gene rs12901499 polymorphism increased the risk of osteoarthritis.

SUBMITTER: Yang HY

PROVIDER: S-EPMC6048206 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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SMAD3 gene rs12901499 polymorphism increased the risk of osteoarthritis.

Yang Hao-Yu HY Hu Wen-Hao WH Jiang Tao T Zhao Hui H

Bioscience reports 20180515 3

A growing body of evidence suggested that smad family member 3 gene rs12901499 polymorphism was associated with the risk of osteoarthritis. However, the results of previous studies were conflicting. In the present study, we assessed whether smad family member 3 gene rs12901499 polymorphism was associated with the risk of osteoarthritis by the meta-analysis. We searched in the databases of PubMed, Embase, and CNKI. Pooled odds ratios and 95% confidence intervals were calculated. Sev ...[more]

PMID: 29764993

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Project description:We investigated single nucleotide polymorphism (SNP) of the betaglycan gene (TGFBR3) encoding the TGFβ co-receptor in endometrial cancer (EC) and its association with betaglycan expression. The study group included 153 women diagnosed with EC and 248 cancer-free controls. SNP genotyping and gene expression were analyzed using TaqMan probes. Three out of the eight SNPs tested, i.e., rs12566180 (CT; OR = 2.22; 95% CI = 1.15-4.30; p = 0.0177), rs6680463 (GC; OR = 2.34; 95% CI = 1.20-4.53; p = 0.0120) and rs2296621 (TT; OR = 6.40; 95% CI = 1.18-34.84; p = 0.0317) were found to be significantly associated with increased risk of EC (adjusted to age, body mass index, menarche and parity). Among the analyzed SNPs, only rs2296621 demonstrated the impact on the increased cancer aggressiveness evaluated by the WHO grading system (G3 vs. G1/2, GT-OR = 4.04; 95% CI = 1.56-10.51; p = 0.0026; T-OR = 2.38; 95% CI = 1.16-4.85; p = 0.0151). Linkage disequilibrium (LD) analysis revealed high LD (r2 ≥ 0.8) in two haploblocks, constructed by rs2770186/rs12141128 and rs12566180/rs6680463, respectively. In the case of C/C haplotype (OR = 4.82; 95% CI = 1.54-15.07; p = 0.0116-Bonferroni corrected) and T/G haplotype (OR = 3.25; 95% CI = 1.29-8.15; p = 0.0328-Bonferroni corrected) in haploblock rs12566180/rs6680463, significantly higher frequency was observed in patients with EC as compared to the control group. The genotype-phenotype studies showed that SNPs of the TGFBR3 gene associated with an increased risk of EC, i.e., rs12566180 and rs2296621 may affect betaglycan expression at the transcriptomic level (rs12566180-CC vs. TT, p < 0.01; rs2296621-GG vs. TT, p < 0.001, GT vs. TT, p < 0.05). Functional consequences of evaluated TGFBR3 gene SNPs were supported by RegulomeDB search. In conclusion, polymorphism of the TGFBR3 gene may be associated with an increased EC occurrence, as well as may be the molecular mechanism responsible for observed betaglycan down-regulation in EC patients.

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SMAD3 gene rs12901499 polymorphism increased the risk of osteoarthritis.

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<i>SMAD3</i> gene rs12901499 polymorphism increased the risk of osteoarthritis.

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