Risk factors for osteoarthritis: genetics11Supported by Procter & Gamble Pharmaceuticals, Mason, OH

Abstract

Although the multifactorial nature of osteoarthritis (OA) is well recognized, genetic factors have been found to be strong determinants of the disease. Evidence of a genetic influence of OA comes from a number of sources, including epidemiological studies of family history and family clustering, twin studies, and exploration of rare genetic disorders. Classic twin studies have shown that the influence of genetic factors is between 39% and 65% in radiographic OA of the hand and knee in women, about 60% in OA of the hip, and about 70% in OA of the spine. Taken together, these estimates suggest a heritability of OA of 50% or more, indicating that half the variation in susceptibility to disease in the population is explained by genetic factors. Studies have implicated linkages to OA on chromosomes 2q, 9q, 11q, and 16p, among others. Genes implicated in association studies include VDR, AGC1, IGF-1, ER alpha, TGF beta, CRTM (cartilage matrix protein), CRTL (cartilage link protein), and collagen II, IX, and XI. Genes may operate differently in the two sexes, at different body sites, and on different disease features within body sites. OA is a complex disease, and understanding its complexity should help us find the genes and new pathways and drug targets.

Osteoarthritis revisited: a contemporary review of aetiology

“…Both familial and twin studies find support for genetic influences on the formation of osteoarthritis (e.g. Jonsson et al, 2003;Manek et al, 2003;Spector & MacGregor, 2004;Zhai et al, 2004;Min et al, 2005). Results from various twin and familial studies show that overall heritability of osteoarthritis averages around 0.50; in other words, 50% of phenotypic variability in osteoarthritis can be accounted for by differences in genotype (e.g.…”

“…Results from various twin and familial studies show that overall heritability of osteoarthritis averages around 0.50; in other words, 50% of phenotypic variability in osteoarthritis can be accounted for by differences in genotype (e.g. Ingvarsson et al, 2000;Lanyon et al, 2000;Jonsson et al, 2003;Manek et al, 2003;Spector & MacGregor, 2004). However, it is important to note that there is research suggesting that twin studies may overestimate heritabilities (Zhai et al, 2004).…”

Prevalence of the Pro12Ala missense mutation in the PPARG2 gene in Kuwaiti patients with primary knee osteoarthritis

“…Osteoarthritis (OA) is a prevalent joint disease and is a leading cause of disability. Although the exact etiology and pathogenesis of OA are not fully understood, epidemiological and genetic studies indicate that genetic factors are strong determinants in the onset of OA 12. A genetic contribution to OA has been suggested in several epidemiological studies 3.…”

Functional variants within the secreted frizzled-related protein 3 gene are associated with hip osteoarthritis in females

“…165720) is the most prevalent form of arthritis and a common cause of disability. Epidemiological studies have demonstrated a major genetic component to primary OA, with estimated heritability of 40% for the knee, 60% for the hip, and 65% for the hand (1). Several genome-wide linkage scans have been performed on cohorts of affected sibling pairs or affected relative pairs concordant for hip, knee, or hand OA (reviewed in refs.…”