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.
ABSTRACT
OBJECTIVE: To explore the associations between vitamin D receptor (VDR) gene Tru9I polymorphism and myasthenia gravis (MG). METHODS: A total of 302 MG patients, diagnosed and treated at Affiliated Hospital of Medical College, Qingdao University and Beijing Friendship Hospital from December 2006 to July 2010, were recruited. And 283 normal subjects were selected as the controls. Tru9I polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The frequencies of genotypes and alleles were compared among different MG subgroups and control group. The relationship between the genotype and susceptibility or severity of MG and immediate efficacies of glucocorticoid were explored. The SPSS17.0 was applied to statistical analysis. RESULTS: In the MG patients whose age of onset was above 15 years, the frequency of TT and tt genotypes in females was lower than that of the control group. However the frequency of Tt genotype was higher than that of the control group. And there were significant differences (χ(2) = 8.847, P = 0.012). The frequency of Tt + tt genotype in females (58/139, 41.7%) was higher than that of the control group (56/189, 29.6%). And there were also significant differences (OR = 1.70, 95% CI 1.07 - 3.41, χ(2) = 5.169, P = 0.023). Although the frequency of t alleles in females (61/278, 21.9%) was higher than that of the control group (65/378, 17.2%), no significant differences existed (P > 0.05). There were no differences in frequencies of genotypes and alleles between the patients with varying severity and different immediate efficacies of glucocorticoid (P > 0.05). CONCLUSION: VDR gene Tru9I polymorphism may be related to the risk of MG in females aged above 15 years.
