Abstract
Osteoarthritis (OA) is a common chronic joint disease affected by environmental and genetic factors. The LTBP3 gene may be involved in the occurrence and development of OA by regulating TGF-β activity and the TGF-β signaling pathway. A total of 2780 study subjects, including 884 hip OA cases and 1896 controls, were recruited. Nine tag single-nucleotide polymorphisms (SNPs) located within the LTBP3 gene region were selected for genotyping. Genetic association analyses were performed at both the genotypic and allelic levels. GTEx data were extracted to investigate the functional consequence of significant SNPs. SNP rs10896015 was significantly associated with the risk of hip OA at both the genotypic (P=0.0019) and allelic levels (P=0.0009). The A allele of this SNP was significantly associated with a decreased risk of HOA (OR [95%CI] = 0.79 [0.69–0.91]). This SNP was also significantly associated with the clinical severity of hip OA. SNP rs10896015 could affect the gene expression of 11 genes, including LTBP3, in multiple human tissues based on GTEx data. We obtained evidence for a genetic association between the LTBP3 gene and hip OA susceptibility and clinical severity based on Chinese Han populations. Our findings replicated the association signals reported by a recent genome-wide association study and deepen the basic understanding of osteoarthritis pathology.
Highlights
Osteoarthritis (OA) is a common chronic joint disease characterized by primary or secondary degeneration of articular cartilage and bone hyperplasia [1]
We further examined the association between single-nucleotide polymorphism (SNP) rs10896015 and KL grading scores in the hip OA (HOA) patients
We explored SNP rs10896015 in the GTEx database and identified that the genotypes of this SNP were significantly associated with the gene expression of latent TGF-β binding protein3 (LTBP3) in various human tissues (Supplementary Table S3 and Figure 2)
Summary
Osteoarthritis (OA) is a common chronic joint disease characterized by primary or secondary degeneration of articular cartilage and bone hyperplasia [1]. Articular cartilage degeneration is the earliest and most important pathological change [2]. The most common pathological changes of OA occur in the knee joint and hip joint. Similar to other chronic and complex diseases, HOA is affected by environmental and genetic factors. Age and gender can influence the incidence of HOA, and multiple genetic studies have confirmed the importance of genetic factors [5]. Twin and family studies indicated that the heritability for HOA is approximately 60% [6]. It is necessary to identify the genes responsible for susceptibility to HOA through candidate gene studies
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