The First Part Of The ZP4 Gene Single Nucleotide Polymorphism And The Chinese Han Population With Primary Open Angle Glaucoma. The Second Part Of A Genetic Stress Susceptibility Peripheral Neuropathy Family Candidate Gene PMP22 Screening Study

Objective: To date,based on the genome-wide association study has identified dozens of genes or loci associated with the pathogenesis of Primary Open-angle Glaucoma.POAG's several pathogenic genes have been identified,such as myocilin,optineurin,WD repeat domain 36,and neurotrophin-4.Recently,researcher founded that the Single Nucleotide Polymorphisms sites rs547984,rs540782,rs693421,and rs2499601,which are located in the Zona Pellucida Glycoprotein 4 gene,are associated with POAG(Nakano M et al.,2009;Kim K et al.,2014).However,there is no relevant evidence about the ZP4 gene associated with POAG in other people.This study examined the association of ZP4 gene SNPs with POAG in a Han Chinese Population.Methods: This study used 336 cases of POAG and 768 normal controls for a case-control study.Four single-nucleotide polymorphisms of ZP4 gene,including rs547984,rs540782,rs693421 and rs2499601,were genotyped by the dye terminator-based SNa Pshot method.The statistical analysis method(SPSS22.0)includes: Chi-square test was used to analyze allele and genotype frequency distribution and analyze their dominant and recessive genetic models;Logistic regression was used to verify the differences in gender and age;using Bonferroni correction to just P values for multiple testing;Haploview4.2(Broad Institute,Cambridge,MA)was used to analysised the linkage disequilibrium and haplotype.Results: The four SNPs genotype frequency of ZP4 were accordanced with HWE in case group and control group(P> 0.05),explained that the objects of research has a group representative.This study did not find that the distribution of alleles of these 4 SNPs in the ZP4 gene was associated with the pathogenesis of POAG.Further used of dominant and recessive genetic models to analyze the relationship between these SNPs sites and POAG,the results showed that the difference was not statistically significant between the case group and the normal control group(P> 0.05).Analysis of haplotypes which produced by these 4 SNPs,the results showed that the distribution of GGAG haplotype was statistically different between the case group and the control group(P<0.05).It was a risk haploid type;individuals with tne GGAG haplotype have a 2.935-fold increased possibility of suffering POAG.Conclusion: In this study,we conducted a case-control study among 336 cases of patients with POAG and 768 healthy controls,to verified the association of POAG and polymorphisms in the four loci of ZP4(rs547984,rs540782,rs693421,rs2499601).The results showed that there were no statistical correlation between the rs547984,rs540782,rs693421,rs2499601 and the incidence of POAG in a Han Chinese Population.Objective: A family of hereditary neuropathy with liability to pressure palsy(HNPP)was screened for defects in the peripheral nerve myelin protein 22 gene.Determine whether the PMP22 gene is the genetic cause of the proband.Methods:(1)Using PCR-Sanger sequencing to screen the mutations in PMP22 gene on 2-5 exon and 5'-UTR flanking regions for the proband and healthy family member.(2)Multiplex ligation-dependent probe amplification(MLPA)was used to detect the duplication or deletion of the large fragment of PMP22 gene.Results:(1)In PMP22 exon and its flanking regions have not found mutation by Sanger sequencing;(2)MLPA have found the relative peak area ratio of PMP22 exon was less than 0.7,indicating that the corresponding17p11.2 fragment containing PMP22 gene had heterozygous deletion.Conclusions: Studies have shown that 17p11.2 large fragments including PMP22 gene deletion is the molecular diagnostic basis for this HNPP proband.