Background Vitamin D receptor (VDR) gene plays an important role in bone mass regulation and demonstrated in human articular chondrocytes of cartilage. We have previously shown a beneficial effect of vitamin D supplementation on symptomatic improvement in OA knee patients.
Objectives This study investigated whether the clinico-radiological response to vitamin D was modulated by VDR gene polymorphisms.
Methods Thisrandomized placebo-controlled trial included 85 cases of Osteoarthritis knee patients as per ACR guideline having vitamin D insufficient level (25(OH) D≤50 nmol/L). Enrolled cases were randomly allocated in placebo (42) and vitamin D supplementation group (43). Clinical OA outcome: pain, stiffness and functional disability were recorded by knee-specific WOMAC index. Radiological grading was done by KL grades. In addition, four individual radiological features (IRF)- joint space width, osteophyte, subchondral sclerosis and tibio femoral alignment were also recorded separately. The serum levels of vitamin D were assessed by a method Enzyme Linked Immunosorbent Assay using IDS kit. Detection of VDR gene polymorphisms (Taq1 & Apa I) were done by PCR-RFLP technique. 25 (OH) D levels, clinical and radiological features were recorded at baseline and at one year follow up.
Results At one year, VDR gene polymorphisms- ApaI and TaqI were associated with changes in 25(OH)D level, clinical and radiological features of disease in both group. At final follow up, in vitamin D supplemented group, TT genotype of TaqI polymorphism shown the maximum increment in the level of 25(OH)D in comparison to Tt and tt genotype whereas in placebo group it remained same. No such association was found in case of ApaI polymorphism.
In clinical features, pain was significantly increased in Tt and tt genotype of placebo group whereas decreased in each genotype of vitamin D supplemented group but not significant at one year follow up. Functional disability and Total WOMAC scores was improved in each genotype of vitamin D supplemented group but significant only in case of Tt genotype (p<0.05) and WOMAC scores in TT genotype also (p<0.05). Out of four individual radiological features, significant decreased Medial JSW was observed in tt genotype and increased Osteophyte scores was observed in TT and Tt genotype of placebo group at one year of follow up. No significant changes were noticed in vitamin D supplemented group.
The least improvements were observed in the tt genotypes. No similar effect was observed with ApaI polymorphism.
Conclusions VDR gene polymorphisms influence the clinico-radiological response to vitamin D supplementation in Osteoarthritis knee
References Tetlow LC, Woolley DE. Expression of vitamin D receptors and matrix metalloproteinases in osteoarthritic cartilage and human articular chondrocytes in vitro. Osteoarthritis Cartilage 2001;9:423–31.
Uitterlinden AG, Fang Y, van Meurs JB, van Leeuwen H, Pols HA. Vitamin D receptor gene polymorphisms in relation to vitamin D related disease states. J steroid Biochem Mol Biol 2004; 89-90:187-93.
Acknowledgements The authors wish to thank Indian Council of Research (ICMR), Delhi, India for providing the financial assistance.
Disclosure of Interest None Declared
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