Abstract
ObjectivesOur aims were to replicate some previously reported associations of single nucleotide polymorphisms (SNPs) in five genes (A2BP1, COG5, GDF5, HFE, ESR1) with hand osteoarthritis (OA), and to examine whether genes (BCAP29, DIO2, DUS4L, DVWA, HLA, PTGS2, PARD3B, TGFB1 and TRIB1) associated with OA at other joint sites were associated with hand OA among Finnish women.DesignWe examined the bilateral hand radiographs of 542 occupationally active Finnish female dentists and teachers aged 45 to 63 and classified them according to the presence of OA by using reference images. Data regarding finger joint pain and other risk factors were collected using a questionnaire. We defined two hand OA phenotypes: radiographic OA in at least three joints (ROA) and symptomatic DIP OA. The genotypes were determined by PCR-based methods. In statistical analysis, we used SNPStats software, the chi-square test and logistic regression.ResultsOf the SNPs, rs716508 in A2BP1 was associated with ROA (OR = 0.7, 95% CI 0.5–0.9) and rs1800470 in TGFB1 with symptomatic DIP OA (1.8, 1.2–2.9). We found an interaction between ESR1 (rs9340799) and occupation: teachers with the minor allele were at an increased risk of symptomatic DIP OA (2.8, 1.3–6.5). We saw no association among the dentists. We also found that the carriage of the COG5 rs3757713 C allele increased the risk of ROA only among women with the BCAP29 rs10953541 CC genotype (2.6; 1.1–6.1). There was also a suggestive interaction between the HFE rs179945 and the ESR1 rs9340799, and the carriage of the minor allele of either of these SNPs was associated with an increased risk of symptomatic DIP OA (2.1, 1.3–2.5).ConclusionsOur results support the earlier findings of A2BP1 and TBGF1 being OA susceptibility genes and provide evidence of a possible gene-gene interaction in the genetic influence on hand OA predisposition.
Highlights
Osteoarthritis (OA) shows clinical heterogeneity in localization and progression [1]
Of the single nucleotide polymorphisms (SNPs), rs716508 in ataxin 2-binding protein gene (A2BP1) was associated with radiographic OA (ROA) (OR = 0.7, 95% CI 0.5–0.9) and rs1800470 in TGFB1 with symptomatic distal interphalangeal (DIP) OA (1.8, 1.2–2.9)
We found an interaction between estrogen receptor 1 alpha (ESR1) and occupation: teachers with the minor allele were at an increased risk of symptomatic DIP OA (2.8, 1.3–6.5)
Summary
Osteoarthritis (OA) shows clinical heterogeneity in localization and progression [1]. Patients may have only one affected joint (monoarthritis) at the time of diagnosis, several affected joints within a single region (e.g. in hand OA), or several involved joints at various sites, e.g. the hip, knee, and hand (polyarticular OA, generalized OA). Twin and family studies have demonstrated a significant contribution of genetic factors that account for up to half of the risk of developing OA [2,3]. The simultaneous involvement of multiple hand joints makes hand OA a heterogeneous disorder that is complex to study [5]. Hand OA, largely mirroring the generalized OA variant, is thought to be more heritable than hip or knee OA [3,6]. It is generally accepted that as a complex disorder, the development of hand OA is modulated by many genes with small effects and gene-environment interaction. The genetic influence may involve either a structural defect (e.g., in collagen), alterations in the structural extracellular matrix (ECM) proteins of cartilage and bone, an enhanced inflammatory component in the disease process, or a genetic influence on a known risk factor for OA, such as obesity [7]
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