The Expression And Related Clinical Studies Of Variants In MEIS1,BTBD9 With Restless Legs Syndrome In Northern Han Chinese Population

[Backgrounds]Restless legs syndrome is a common sensorimotor neurological disorder,Its clinical symptoms is characterized by acid、paraesthesia、paining、crawling、itching and other uncomfortable sensations in the legs,patients were forced to beat、activity body,or out of bed to walking to relieve the abnormal fellings,which made worse during rest or inactivity,especially in the evening or night,sleep is disturbed and serious affect the quality of life.Until now,the pathogenesis of RLS is still unknown.Studies suggest that the main pathogenesis is the dopaminergic neurons dysfunction of the central nervous system.At the same time,iron,opioids and gamma-aminobutyric acid(GABA)neurotransmitter involved.Some studies show that RLS has highly positive family rates and with more apparent in twin studies,speculating has genetic susceptibility.Risk genes,environmental factors and their interactions are involved in its pathogenesis.So far,Genome-wide association studies in different races found six susceptibility genes are related with its pathogenesis(MEIS1,BTBD9,PTPRD,MAP2K5,LBXCOR1/SKOR1,TOX3).MEIS1 and BTBD9 in the pathogenesis of RLS have researched in animal models.Currently there is no reports of death and disability with RLS,which has serious effects on physiological functions.researchs shows relationships with anemia,renal failure,hypertension,coronary arteriosclerosis heart disease,cerebrovascular disease and so on.Studies on potential factors affecting RLS severity are quite limited.[Objectives]1.Explore the relationship of susceptibility genes MEIS1 rs2300478,BTBD9 rs3923809 with restless legs syndrome in Northern Han Chinese Population,promoting the understanding of the molecular pathogenesis;2.Discusse the correction of RLS onset age,duration and RBC,hemoglobin,serum iron,serum ferritin levels with the severity of RLS,finding the potential factors affected the severity.[Contents]1.The susceptibility genes MEIS1 rs2300478 and BTBD9 rs3923809 genotype and allele frequency in Northern Han Chinese Population with RLS;2.RLS onset age.duration and RBC,hemoglobin,serum iron,serum ferritin levels and the relationships with the severity.[Methods]1.Collect the blood specimens of RLS patients,all from clinical neurology out-patient and in-patient in the second hospital of shandong university from 2016.4 to 2016.12.Inclusion criteria:all the patients were following the standardized criteria which developed in 1995 by the International RLS Study Group(IRLSSG)and revised in 2012.All were signed informed consent.According to the International RLS Study Group Rating Scale(IRLSSGRS)to assess the severity of RLS.2.The control group:all from healthy adults doing health physical examination in the second hospital of shandong university.Inclusion criterias:①without anemia,renal insufficiency,hyperglycemia,hypertension,hypothyroidism,migraine,arthritis,peripheral neuropathy and other chronic diseases;②without pregnancy or lactation;③without dopaminergic or anti dopaminergic drugs,sympathetic,antidepressants,sedatives,antiepileptic,benzodiazepines,clonidine,folic acid,magnesium,ferrous salt,lithium,antihistamines,metoclopramide used in recently 14d;④No depression and anxiety,movement disorders,mental disorders.3.Collect objects’ EDTA anticoagulant peripheral blood 2-3ml,extraction of genomic DNA,TaqMan probe detection BTBD9 rs3923809,MEIS1 rs2300478.4.Using the spss17.0 software for statistical analysis.the Quantitative datas use Mean±standard deviation(Mean±S),the count data with rate(%).The Hardy-weinberg equilibrium tested in the control and case groups.genotype and allele frequency distribution is estimated by the Chi-square test.Calculate the odds ratio and 95%confidence interval for the different genotype effects.potential factors with RLS severity are estimated by single factor analysis of variance.P<0.05 statistically significant.[Results]1.97 RLS cases of which including 51 men and 53 women,with an average age of 60.31± 12.81years.Control group has 112 cases,which included 51 males and 61 females and the average age is 57.36± 10.3years,there is no statistical difference in age and sex between two groups.2.According to the International Restless legs syndrome rating scale(IRLSSGRS)cIassified the severity,mild 21 in 97 RLS cases and Moderate 55 5 21 cases of severe and very severe 0 cases;.3.The distribution of GG,GT and TT in MEIS1 rs2300478 and the risk allele G have no statistically difference from that in control group and case group;4.The genotypes distribution of AA,AG and GG in BTBD9 rs3923809 and the risk allele A have no statistical difference between the control and case group;5.RLS onset age and severity have no statistical difference in genetype of MEIS1 rs2300478 and BTBD9 rs3923809;6.The blood erythrocyte,hemoglobin,serum iron and ferritin levels have no relationship with the severity of RLS.7.The total severity score isn’t associated with the onset age of RLS,and influenced by the disease duration.[Conclusions]1.Susceptibility genes MEIS1 rs2300478,BTBD9 rs3923809 have no relationship with restless legs syndrome,MEIS1 rs2300478 and BTBD9 rs3923809 are not susceptibility genes of restless legs syndrome in Northern Han Chinese Population.2.The genetype of MEIS1 rs2300478,BTBD9 rs3923809 have no relationship with the RLS onset age and severity.3.The severity of restless legs syndrome in Northern han Chinese population have no relationship with red blood cells,hemoglobin,serum iron and ferritin levels;4.The total severity score isn’t associated with the onset age of RLS,and influenced by the disease duration.