Vitamin D receptor genotype is associated with radiographic osteoarthritis at the knee.

Abstract

Osteoporosis and osteoarthritis are age-related disorders of the skeleton with genetic components. Low bone density is a risk factor for osteoporotic fracture while osteoarthritis is associated with increased bone density. The 1,25-dihydroxyvitamin D 3 receptor (VDR) gene locus was previously found to be associated with bone density. We therefore studied the relationship between radiographic osteoarthritis at the knee and VDR genotype in a population-based sample ( n ϭ 846), using molecular haplotyping of anonymous intragenic DNA polymorphisms. Radiographic osteoarthritis was defined using the Kellgren score, which is based on the assessment of osteophytes and joint space narrowing (JSN). We show that one VDR haplotype allele is significantly overrepresented in individuals with knee osteoarthritis and associated with a 2.27-fold increased relative risk (95% confidence interval 1.46, 3.52). Adjustment for bone density at the femoral neck did not change these results, indicating that the association is not mediated by bone density. The association appeared to be largely explained by the presence of osteophytes rather than JSN. Our results indicate a role of the VDR gene in the pathogenesis of osteophytes while linkage disequilibrium with another nearby gene, i.e., the collagen type IIa1 gene encoding the most abundant protein in cartilage, might contribute to the association. ( J. Clin. Invest. 1997. 100:259-263.)

Identification of sequence polymorphisms in two sulfation-related genes, PAPSS2 and SLC26A2, and an association analysis with knee osteoarthritis

“…The true pathogenesis of OA resides in degeneration and subsequent loss of articular cartilage, however; osteophytes only reflect the reactive change. The dominance of osteophytes in diagnosing radiographic OA using the Kellgren scale has been pointed out (Hart and Spector 1995;Uitterlinden et al 1997). In contrast, our new three-part scale emphasizes joint-space narrowing and estimates the severity of osteophytes independently.…”

An Investigation Into the Relationship Between Taq1 and Apa1 Polymorphisms of the Vitamin D Receptor Gene and the Development of Osteoarthritis

“…[21] However, in a study of sporadic prostate cancer in the Turkish population, [22] the VDR gene ApaI polymorphism was found to be associated with the disease. Although, VDR gene polymorphisms were discovered to be associated with hand OA in Finnish women [10] and with radiographic OA in Netherlands, [8] Huang et al [11] did not find any association between VDR gene polymorphisms and hand, hip or knee OA in a Japanese population. This finding is consistent with our results.…”

“…Genetic variants of the VDR gene locus on chromosome 12 are associated with bone density, which was found to increase in patients with OA. [8] Nonetheless, it is still uncertain whether genetic variants of the VDR gene (TaqI and ApaI polymorphisms) are involved in the development of OA. [9][10][11] Since gene pools, lifestyle, and geneenvironment interactions vary between populations, the risk should not be the same with respect to genotypes in every population.…”

The Genetics of Osteoarthritis

“…These genes have been studied in OA, but VDR has received the most attention, and first reports have shown significant associations with an increased risk in the presence of different polymorphisms (Ken et al, 1997;Uitterlinden et al, 1997;Solovieva et al, 2006;Valdes et al, 2006); however, this has not always been confirmed (Aerssens et al, 1998;Baldwin et al, 2002;Huang et al, 2000;Loughlin et al, 2000b). A meta-analysis on the most frequently studied VDR polymorphisms (TaqI, BsmI, and ApaI) in OA analyzed a total of 10 studies of persons of Asian or European origin involving a total of 1,591 patients with OA and 1,781 controls.…”