Genetic Influences on Hand Osteoarthritis in Finnish Women – A Replication Study of Candidate Genes

<div><p>Objectives</p><p>Our 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.</p><p>Design</p><p>We 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.</p><p>Results</p><p>Of the SNPs, rs716508 in <i>A2BP1</i> was associated with ROA (OR = 0.7, 95% CI 0.5–0.9) and rs1800470 in <i>TGFB1</i> 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 <i>COG5</i> rs3757713 C allele increased the risk of ROA only among women with the <i>BCAP29</i> rs10953541 CC genotype (2.6; 1.1–6.1). There was also a suggestive interaction between the <i>HFE</i> rs179945 and the <i>ESR1</i> 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).</p><p>Conclusions</p><p>Our results support the earlier findings of <i>A2BP1 and TBGF1</i> being OA susceptibility genes and provide evidence of a possible gene-gene interaction in the genetic influence on hand OA predisposition.</p>