Pigment Epithelium-Derived Factor GenePolymorphisms In Exudative Age-RelatedDegeneration In A Chinese Cohort

[Purpose] To investigate polymorphisms in the pigment epithelium derived factor (PEDF) gene ina Chinese cohort with exudative age-related macular degeneration (AMD). To study the distribution of genotypes and alleles of PEDF Met72Thr (rs1136287) and-5736T>C (rs12150053), and four tagSNPs (tSNPs) polymorphisms in exudative AMD and healthy control group in a Chinese cohort and the correlation between these polymorphisms and the pathogenesis of AMD.[Method] 168 unrelated Chinese patients with exudative AMD were recruited. There were 95 males and 73 females whose ages ranged from 52 to 86 years with a mean age of 70.9±11.3 years. Two hundred and thirty control participants were also recruited; 134 were male and 96 were female. Their ages ranged from 63 to 92 years, with a mean age of 74.4±9.6 years. The mean age of the patients with neovascular AMD was slightly lower than that of control participants. The patient and control participants were matched for ethnicity, age, and sex。Genomic deoxyribonucleic acid (DNA)was extracted from exudative AMD patients and healthy control subjects, The genotypes of PEDF Met72Thr (rs1136287) and-5736T>C (rs12150053), and four tagSNPs (tSNPs) were detected by polymerase chain reaction。SNP genotyping was performedusing the MassARRAY system (Sequenom)by means of matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry. Genotype was analyzed using the MassARRAY Typer software version 3.4 (Sequenom). A different tester duplicated the genotyping of a random 10% of the sample and the reproducibilityof the results was found to be 100%. The differences in the clinical baseline data between patient and control participants were analyzed using the Student's t-test and chi-square test. Hardy-Weinberg equilibrium (HWE) for the genotype frequencies was verified by the chi-square test. The association studies were performed with SPSS 14.0 for Windows (SPSS,Chicago, Illinois, USA). The frequencies of alleles between the two groups were estimated using the chi-square test.Odds ratios (ORs) and their corresponding 95% confidence intervals (Cls) were calculated for ascertained genotypes, alleles, and haplotypes due to the polymorphisms in the PEDF genes. The criterion for statistical significance was p<0.05.[Result]1,The observed genotype frequencies of PEDF genotypes in age-related macular degeneration patients did not show any significant differences between the patient and control groups.rs12150053 T/C OR (95%CI) 1.22(0.89-1.68), p= 0.22, rs11658342 G/A OR (95%CI) 0.96(0.70-1.33), p=0.82; rs1136287 C/T OR (95%CI) 0.92(0.69-1.22), p=0.56; rs1894286 C/T OR (95%CI) 1.12(0.76-1.64), p=0.57; rs2269344 C/G OR (95%CI) 0.93(0.65-1.32), p=0.67; rs9889773 G/A OR (95%CI) 1.02(0.77-1.35), p=0.922,According to the genotype distribution for these candidate SNPs of PEDF, only heterozygous CT of rs1136287 exerted a protective effect against exudative AMD (OR 0.59, CI 0.36-0.95, p=0.03)3,Haplotype association analysis:Haplotye TG(χ2=0.723 p=0.395)and CA(χ2=0.65,p=0.420) according to rs12150053 and rs11658342did not provide any evidence for an association with the risk of exudative AMD. Haplotye CG (χ2=0.06,p=0.809),CA (χ2=0.396, p=0.529),GA (χ2=0.09, P=0.763) according to rs2269344 and rs9889773did not provide any evidence for an association with the risk of exudative AMD.[Conclusions]1. Each PEDF gene polymorphism exhibited HWE except for rs1136287 in the control group (p<0.05); it was, therefore, retained for furtheranalysis.2,No association was found in the allele frequencies of any individual SNP between these two groups. According to the genotype distribution for these candidate SNPs of PEDF, only heterozygous CT of rs1136287 exerted a protective effect against exudative AMD. Therefore, no evident association was found between the genotype frequencies of any individual SNP and susceptibility to the disease. Haplotype analyses of the SNPs in this study did not provide any evidence for an association with the risk of exudative AMD in this Chinese cohort.3,No evidence was found to support the hypothesis that SNPs of the PEDF gene contribute to susceptibility to exudative AMD. Further studies towardsthe elucidation of the role of PEDF gene variations in the pathogenesis of exudative AMD are required.