Study On Iron Deposition In The Substantia Nigra Of Parkinson’s Disease In Han Chinese Population

Objective: To investigate the relationship between Divalent metal transporter 1(DMT1)gene variants,serum iron,transferrin,C-reactive protein(CRP)and ceruloplasmin(CP)and iron deposition in the substantia nigra of idiopathic Parkinson’s disease.Methods: A case-control study was carried.120 PD patients who matched for gender and age were recruited and were divided into positive group(67 patients)and negative group(53 patients).DNA was isolated from peripheral blood through standardized phenol/chlorine extraction method.For all subjects the gene mutation/polymorphisms at DMT1 1303C/A,1254T/C,IVS4 + 44C/A,rs6580779 locus were analyzed by PCR-RFLP method.Results of serum iron,transferrin,C-reactive protein(CRP)and ceruloplasmin(CP)were analized.Results: 1.For the 1303C/A,C → A mutation at 1303 nucleotide was not found in all PD patients in both groups.2.The SNP 1254T/C allele polymorphism was found with the combination of three genotypes TT/TC/CC.The three genotype frequency in positive group was was77.6%、22.4% and 0%,while in negative group was81.8%、15.1% and 3.8%.The T/C allele frequencies were 88.8%、11.2% and 88.7%、11.3% respectively.3.There are three different combinations of genotypes CC/CA/AA for IVS4 + 44C/A locus,no any significant association was found in the tested genotypes,alleles or mutations between the positive and negative groups.In the positive group the frequency of genotypes was76.1%,23.9% and 0% while they were 79.2%,17%,3.8% in the negative group,the frequency of minor allele was 11.9%,12.3% respectively.4.For SNP rs6580779 locus,there are only two types of genotype which are AA/AC,no significant association was obtained in the tested genotypes,alleles or mutations between the positive and negative groups either.In the positive group the frequency of genotypes was98.5%,1.5% while they were 94.3%,5.7% in the negative group,the frequency of minor allele was 0.8%,2.8% respectively.5.No association was found even when logistic regression was adopted for age and gender and analysis after stratification by age onset further.6.No significant difference was found when compared the levels of serum iron,transferrin,C-reactive protein and ceruloplasmin between positive group and negative group.The male patients or patients in the middle and advanced stage in positive group had lower serum ceruloplasmin than those in the negative group.The level of serum transferrin in positive group was related to H-Y stages negatively.Males in the positive group had lower serum transferrin than femals,the serum transferrin reduced as the growth of age in the positive group.The level of serum iron correlated to the H-Y stage negatively,while the level of serum iron or tranferrin correlted to H-Y stages negatively.Conclusion: 1.There was no significant association between DMT1 gene 1303C/A,1254T/C,IVS4 + 44C/A,rs6580779 locus variation in PD patients grouped by the different results of ultrasound as prospectively.2.There was no difference between iron-related clinical markers and iron accumulation in the substantia nigra.Serum iron correlated with Hoehn and Yahr stage negatively.In the positive group,males or patients in middle and advanced stage had lower serum ceruloplasmin,and males or older or patients in the late stage had lower serum transferrin.