Association Of Mtnr1aand Mtnr1b Gene Polymorphisms With Systemic Lupus Erythematosus In A Chinese Population

BackgroundSystemic lupus erythematosus?SLE?is a chronic autoimmune disease.It is characterized by the stimulation of self-antigen and the production of excessive self-antibodies,involving multi-system organs.At present,there is a significant difference in the incidence of SLE between different regions,races and genders.The majority of SLE patients are women,with a male to female ratio of 1:9,and the majority of the onset age is 20⁴5 years old.The etiology and mechanism of SLE are not clear and may be affected by genetic and epigenetic factors.Melatonin receptors?MTNR?are transmembrane proteins of the GPCR superfamily,mainly found in the brain,gastrointestinal,retina,kidney,immune system and reproductive system.In mammals,the MTNR has the MTNR1A and MTNR1B subtypes.Some studies have shown that the MTNR1B gene polymorphism is associated with rheumatoid arthritis.At present,the studies are limit which involved on the association between melatonin receptor gene polymorphism and SLE susceptibility in Chinese Han population.ObjectiveThe study was detected to explore the association of single nucleotide polymorphisms?SNPs?of mtnr1a andmtnr1bwith the susceptibility of SLE patients in Chinese Han population.The relationship between SNPs of mtnr1a,mtnr1band patients'main clinical symptoms was analyzed.The association of mtnr1aandmtnr1b gene polymorphisms with plasma MLT levels in SLE patients was compared.MethodsA case-control study was conducted.A total of 495 patients with SLE and 493healthy volunteerswere recruited.SNPscan^TM genotyping technique was used to analyze the correlations between mtnr1a?rs10030173,rs2119882,rs2165667,rs4861722,rs6847693?,mtnr1b?rs10830962,rs12804291,rs1562444,rs3781637?polymorphisms and major clinical symptoms.We tests the association of melatonin levels in serum with mtnr1a,mtnr1b gene polymorphisms in SLE patients were detected by ELISA.ResultsNo significant differences were observed for the distribution of genotype frequencies and allele of 9 SNPs between SLE patients and healthy volunteers?all P>0.05?.The genotype effects of mutation model,wild model,additive model were further analyzed.There was no significant difference in the distribution between SLE patients and healthy volunteers?allP>0.05?.Our study were explored the association between mtnr1a,mtnr1b gene polymorphisms and the main clinical features of SLE patients.In SLE patients with malar rash,the frequency of CC and GC genotypes of mtnr1brs10830962 was higher than patients without arthritis??2=7.904,P=0.018?.In SLE patients with arthritis and high activity,the A allele frequency of the mtn1rb rs1562444 was higher than patients without arthritis and high activity??2=5.112,P=0.024;?2=4.238,P=0.040?.There was no significant difference in the distribution of haplotypes of mtnr1a,mtnr1b between SLE patients and healthy volunteers?bothP>0.05?.Serum MLT levels had a significant association with the mtnr1b rs1562444 in SLE patients?P=0.001?.Conclusions9 SNPs of mtnr1a,mtnr1b genes were not associated with SLE susceptibility.Partial SNPs may be associated with certain clinical features of SLE.Serum MLT levels is associated with mtnr1b rs1562444.