Association Study Both The MMP2and COL9A2Gene With Pathological Myopia In400Cases Han Chinese Population

Objective:1. To investigate association between the matrix metallopeptidase2(MMP2)and Collagen Type IX Alpha2(COL9A2）gene single nucleotide polymorphism withpathological myopia in a Chinese Han population；2. Mutation analysis of the MMP2andCOL9A2gene.Methods：Four hundred unrelated patients with pathological myopia and four hunderdnormal controls in a Han Chinese population were studied. All the subjects were genotypedfor20tag single nucleotide polymorphisms (SNPs) in MMP2with SNaPshot method.Screening for mutations in the coding regions and the adjacent intronic regions of MMP2gene was performed in200patients with pathological myopia and200normal controls bySanger sequencing.Mutation screening of all exons of the COL9A2gene was performed by Sangersequencing in200subjects with pathological myopia (Cases1) and200normal controls(Controls1). The tested mutaions were genotyped by SNaPshot method in another200cases (Cases2) and200normal controls (Controls2).Results: None of the20tag SNPs showed significant association with pathologicalmyopia in this study. Seven variations were detected upon sequencing of the codingregions and the adjacent intronic regions of MMP2in200subjects with pathologicalmyopia and200normal controls. One novel variation, c.1287G>A, was detected in exon7of MMP2gene in79of the200patients with pathological myopia (65heterozygous and14homozygous) and in84of the200controls (67heterozygous and17homozygous). BySanger sequencing, the c.1810G>A mutation was detected in exon9of MMP2gene inthree of the200patients with pathological myopia but not in the controls. The five othervariations, known as polymorphisms, were detected in the case and control groups.By Sanger sequencing, the reported D281fs frameshift mutation of COL9A2was notfound in the200cases (Cases1) and200normal control (control1). One novel variant,c.143G＞C heterozygous missense mutation in exon2of COL9A2, was identified in one pathological myopia subject and another novel variant，c.884G＞A heterozygous missensemutation in exon17of COL9A2，was found in the other case. None of them were found innormal controls. One SNP (rs2228564) in COL9A2gene was detected in the coding region,and there is no significant allele frequency of rs2228564between the Han Chinese patientsand normal controls (P＞0.05). Gentyping another200cases (Cases2) and200controls(Controls2) by SNaPshot method, the c.143G＞C in one case and c.884G＞A in two caseswere found, and there is also no significant association between cases and controls (P＞0.05).Conclusion: There is no association between the Han Chinese pathological myopia and20tag SNPs in MMP2gene which we tested, the heterozygous missense mutation c.1810G>Ain exon9of MMP2gene may be associated with the patient of pathological myopia.The D281fs frameshift mutation in the COL9A2gene is not associated withpathological myopia in the Han Chinese population. The novel mutations, mutation c.143G＞C in exon2of COL9A2and mutation c.884G＞A in exon17of COL9A2, maycontribute to the development of pathological myopia.