Vitamin D Receptor Polymorphism and Myasthenia Gravis in Chinese Han Population

Abstract

Myasthenia gravis (MG) is an autoimmune disease in which antibodies bind to acetylcholine receptors (AChR) or other functional molecules in the postsynaptic membrane at the neuromuscular junction. Vitamin D (VD) has a number of pluripotent effects, which include immune-regulation and bone metabolism. The immunomodulatory actions of 1,25(OH)2D3 are mediated by its binding to a vitamin D receptor (VDR). In the study, we undertook a case-control study to explore the association between VDR gene polymorphism and the susceptibility and severity of MG patients. Four hundred and eighty MG patients and 487 healthy controls were included and gene polymorphisms of VDR were determined with improved multiplex ligation detection reaction technique and SNPscanTM technique. MG patients were classified into subgroups by essential clinical features and by a comprehensive classification. The frequencies of alleles and genotypes were compared between the MG group and the control group, between each MG subgroup and the control group, and between each pair of MG subgroups. There were no significant differences in frequencies of alleles and genotypes between MG patients and healthy controls, between MG subgroups and healthy controls, or between each pair of MG subgroups in the analysis of subgroups classified by essential clinical features (onset age, gender, thymoma, AChRAb positivity, onset involvement) and the maximal severity (modified Oosterhuis score). In the analysis of subgroups with a comprehensive classification, the frequencies of alleles and genotypes in rs731236 showed significant differences between adult non-thymoma AChRAb negative MG subgroup and the control group, as well as the adult non-thymoma AChRAb positive MG group. In the Chinese Han population, rs731236 was found to be possibly associated with adult non-thymoma AChRAb negative MG patients, although this needs further confirmation.

Vitamin D receptor and binding protein genes variants in patients with migraine

“…Other described associations of SNVs in the VDR gene include an association of VDR rs7975232 and the risk for multiple sclerosis 51 and amyotrophic lateral sclerosis, 52 VDR rs2228570 with ischemic stroke, 53 VDR rs2228570 and VDR rs7975232 with childhood temporal lobe epilepsy, 54 and VDR rs731236 with adult nonthymoma myasthenia gravis with the negativity of acetylcholine receptors antibodies. 55 An association of VDR rs2228570 and VDR rs731236 with the risk for restless legs syndrome reported in one study 41 was not confirmed in another. 56 GC rs7041 SNV has been associated with the risk for Parkinson's disease, 57 while GC rs7041, GC rs4588, and GC rs2282679 were not associated with the risk for multiple sclerosis, 58 and GC rs7041and GC rs4588 were not associated to restless legs syndrome.…”

“…Pooled data of two studies 48,49 showed an association between VDR rs2228570 and essential tremor, while VDR rs731236, 49,50 VDR rs7975232, 49 VDR rs739837, 49 and VDR rs78783628 49 showed lack of association with this disease. Other described associations of SNVs in the VDR gene include an association of VDR rs7975232 and the risk for multiple sclerosis 51 and amyotrophic lateral sclerosis, 52 VDR rs2228570 with ischemic stroke, 53 VDR rs2228570 and VDR rs7975232 with childhood temporal lobe epilepsy, 54 and VDR rs731236 with adult non‐thymoma myasthenia gravis with the negativity of acetylcholine receptors antibodies 55 . An association of VDR rs2228570 and VDR rs731236 with the risk for restless legs syndrome reported in one study 41 was not confirmed in another 56 …”

Vitamin D add on the standard treatment for myasthenia gravis symptoms following total gastrectomy: a case report

“…Some studies have shown that the vitamin D receptor (VDR) acts as a transcription factor and the immunomodulatory impact of 1,25(OH)2D3 is facilitated through its binding to VDR [ 20 ]. Notably, the VDR gene Tru9I (rs757343) polymorphism has been closely linked to the susceptibility of MG in females aged over 15 years [ 21 , 22 ]. Furthermore, in the Chinese Han population, there is a potential association between rs731236 and adult non-thymoma AChRAb-negative MG patients, implying a connection between vitamin D and the onset of MG [ 23 , 24 ].…”