Vitamin D receptor gene BsmI polymorphisms in Thai patients with systemic lupus erythematosus

The importance of genetic influences on systemic lupus erythematosus (SLE) has been recognized through cumulative genetic epidemiologic studies. Many population-based studies have shown associations between the disease and alleles of immunologically relevant genes, including certain major histocompatibility complex (MHC) loci, Fcγ receptor, and cytokines [1]. 1,25-dihydroxyvitamin D3 is thought to exert many of its action through interaction with a specific intracellular receptor. At the molecular level, 1,25-dihydroxyvitamin D3 inhibits the accumulation of mRNA for interleukin (IL)-2, interferon (IFN)-γ, and granulocyte-macrophage colony-stimulating factor (GM-CSF). At the cellular level, the hormone interferes with T helper cell (Th) function, reducing Th induction of immunoglobulin production by B cells. When given in vivo, 1,25-dihydroxyvitamin D3 has been particularly effective in prevention of autoimmune diseases such as experimental autoimmune encephalitis and murine lupus [2]. It has been demonstrated that patients with SLE have a lower level of 25 hydroxyvitamin D3 than do healthy controls [3]. In addition, high-dose 1,25-dihydroxyvitamin D3 and its analog may be useful therapeutic agents for psoriatic arthritis [4] and rheumatoid arthritis [5].Polymorphism of the vitamin D receptor (VDR) gene was found to be associated with many diseases, including osteoporosis [6], hyperparathyroidism [7], and prostate cancer [8]. An association between VDR gene polymorphism and SLE in Japanese and Chinese patients has been reported with mixed results [9-11]. Although Asians are closely related ethnically, the genetic admixture in Japan or China is different from that of Thailand. Because a high prevalence and high clinical severity of SLE are also observed in the Thai population, we examined the characteristics of VDR gene BsmI polymorphisms in a larger cohort of Thai patients with SLE and the relationship of polymorphisms to the susceptibility and clinical manifestation