Studying mevalonate kinase gene polymorphisms in patients with ankylosing spondylitis

Objective: Ankylosing spondylitis (AS) is a chronic, progressive, inflammatory disorder, which generally affects the axial skeletal system. Despite the fact that its etiology is largely unknown, genetic factors have a substantial role in the development of AS. Mevalonate kinase (MVK) is an enzyme involved in cholesterol biosynthesis pathway. The MVK gene mutations are known to be responsible for the pathogenesis of hyperimmunoglobulinemia D and periodic fever syndrome. There is no study investigating the MVK gene polymorphisms in AS patients. In this study, we aimed to examine the MVK gene polymorphisms in AS patients to report its contribution to the pathogenesis, and its effect on the clinical symptoms. Material and Method: A total of 51 AS patients, consisting of 32 male (62.7 %) and 19 female (37.3 %), who are older than 18 years of age and meet the 1984 Modified New York criteria are included in the study. Control group was consisted of age and sexmatched 52 healthy volunteers (31 male and 21 female) who had neither sign of SpA nor the history of systemic autoimmune or autoinflammatory disease. All persons were questioned about symptoms of periodic fever syndrome. Measurements of spinal mobility and physical examination were performed for AS patients. ESR and CRP levels were simultaneously analyzed and recorded. AS patients were asked to fill BASDAI and BASFI forms. IgD levels of patients with AS were carried out by using the radial immunodiffusion assay. After DNA extraction from the peripheral blood samples, PCR/sequence-based typing technique was performed to identify polymorphic sites within the MVK gene. Differences in terms of these polymorphisms were investigated between AS patients and the control group. MVK gene polymorphisms detected in the patient group were further studied with respect to their effects on the clinical symptoms of AS and the type of involvement. Results: The mean age of the patient and control groups was 37,31±10,297 and 33,81±12,367 years respectively. Single nucleotide polymorphisms, named as the first group symptomatic, c.769-38 C>T heterozygote, c.769-7 T>G heterozygote, c.769-38 C>T homozygote were found to have similar frequencies in patient and control groups (p=0,646). The second group, called asymptomatic single nucleotide polymorphisms, were detected in higher number in the AS group compared to the control group (83/58), however the difference was not statistically significant (p>0.05). The newly found single nucleotide polymorphisms, including I56V A>G heterozygote, E281D G>D heterozygote, V80I G>A heterozygote, and C173Y G>A heterozygote were identified in four of AS patients. These polymorphisms could not be found neither during literature search nor in the Infevers website. When all polymorphisms in the MVK gene were evaluated, 36 patients (70.6%) with AS and 33 subjects (%63.4) from control group were found to have single nucleotide polymorphisms. Differences in frequencies were not statistically significant between the groups (p>0.05). There was no difference in the clinical symptoms in AS patients with and without single nucleotide polymorphisms in the MVK gene. Conclusion: The frequency of total MVK gene polymorphisms was found to be higher in AS patients compared to the control group. However, no effect on the clinical symptoms was detected. Further studies with larger number of patients and on different populations should be conducted in order to investigate the reason why the same polymorphisms were found in both groups but in higher proportion in the patient group as well as the impact of these polymorphisms on the clinical signs and symptoms. Four previously unknown single nucleotide polymorphisms were described in this study. Keywords: Ankylosing spondylitis, IgD, Mevalonate kinase gene, Periodic fever,