A prospective cohort study of the association of MTNR1B, MTNR1A polymorphic gene variants with metabolic and sleep disorders during glucocorticoid therapy in patients with multiple sclerosis

Background. Insomnia and metabolic disorders often accompany the use of glucocorticosteroids (GCS). It has been shown that melatonin receptor gene polymorphisms are associated with the listed abnormalities. Previously, associations of polymorphic MTNR1A, MTNR1B variants with insomnia and metabolic changes during GCS therapy have not been determined.

Objective. Evaluation of the association of single nucleotide polymorphisms of the melatonin receptor genes MTNR1A (rs34532313), MTNR1B (rs10830963) with the occurrence of insomnia, the severity of insomnia and metabolic disorders during corticosteroid pulse therapy in patients with multiple sclerosis.

Methods. Patients diagnosed with MS receiving corticosteroids for exacerbation were examined. Fasting blood glucose, lipid profile, and insomnia severity index were monitored before and after therapy. In all patients, MTNR1A (rs34532313) and MTNR1B (rs10830963) gene polymorphisms were determined using real-time polymerase chain reaction. Statistical analysis was performed using the StatTech v. 3.0.9.

Results. The study included 80 patients (71.2% women), mean age 36.26±10.03 years, duration of multiple sclerosis 6 (2.75–10.00) years. A statistically significantly higher level of total cholesterol after GCS (P=0.025), low-density lipoprotein levels before and after GCS therapy (P=0.023 and P=0.010, respectively) were found in the carriers of the G allele rs10830963. Insomnia was more often observed during corticosteroid therapy among patients with CG and GG genotypes (P<0.001), more severe sleep disorders during corticosteroid therapy (P=0.002) were also observed in carriers of the G allele rs10830963 of the MTNR1B gene. The association of rs34532313 MTNR1A with the above parameters was not confirmed.

Conclusion. Carrying the allele G rs10830963 of the MTNR1B gene is associated with insomnia, more severe sleep disorders during corticosteroid therapy, and lipid metabolism disorders. The identified associations may help in further study of the effect of melatonin on the development of metabolic and sleep disorders against the background of corticosteroid therapy.