The Abnormal Expression Of LAMA1 Gene In Blood Of Northern Han Patients With Pathological Myopia

Objective: Pathological myopia (PM) is a kind of ametropia that diopter is more than -6.0(D) with continuous vision deterioration, usually accompanying ocular axis lengthening and ocular fundus changing such as temperal crescent, pigment epithelium thinning, leopard retina, Fuch's macula, retina-choroidal atrophy and so on. PM can cause many comp- lications including amblyopia, glaucoma, cataract, vitreous opacification, retina detachment etc, and become a kind of severe hereditary ocular disease that can lead to blinding. Domestic and overseas researches have confirmed PM's heritage and genetic heterogeneity. Until now we know 10 affirmative gene locus, including Xq28(MYP1), 18p11.31(MYP2), 12q21-q23(MYP3), 7q36(MYP4), 17q21-q22(MYP5), 4q22-q27, 2q37.1, Xq23-q25, 15q12–13, 5p15.33-p15.2. Among all these loci, LAMA1 gene in MYP2 is considered as the candidate gene of PM for its encoding laminin-the structural glycoprotein of sclera, which can link collagen fiber formed by microfibris. The previous study of our group has studied on transcriptional level (mRNA level) of LAMA1 gene in scleral tissue between pathological myopic eyes and non-myopic eyes. The result showed that mRNA level of LAMA1 gene in pathological myopic scleral tissue is significant lower than non-myopia (P<0.01). Therefore, in this study, we still focus on LAMA1 gene for further research. We analyze sequences of the exon27, exon44 in LAMA1 gene of individuals with simple pathological myopia and control subjects of Chinese Northern Han, and then investigate the relationship between LAMA1 gene and single pathological myopia.Methods: 14 individuals with simple PM (all are sporadic patients) were selected and 7 males and 7 females were included, and 16 control subjects were selected (9 males, 7 females). Genomic DNA was collected from 5ml vein blood, then the exon27, exon44 in the LAMA1 gene were analyzed by polymerase chain reaction (PCR) and direct sequencing. Allele frequencies were tested for Hardy-Weinberg equilibrium (HWE). Theχ2 Fisher test was conducted to investigate the genotypic and allelic distri- bution between the PM and control groups.Results: The genotyping success rate was 100%. 7 patients with PM showed one gene mutation in the exon27 of LAMA1 gene: G4090A. This mutation was samesense mutation: glutaminate→glutaminate (50% 7/14 in patients, 0% 0/16 in controls), the genotype distribution: p=0.013, the allele frequency: p=0.006. No gene mutation was identified in the exon44 of LAMA1 gene.Conclusion: As an important candidate gene in MYP2, one gene mutation was found in the exon27 of LAMA1 gene. Thus, there was a relationship between the LAMA1 gene and pathological myopia. However, further studies are needed to confirm finally whether LAMA1 is the virulence gene of PM, and how mutation in LAMA1 gene acts in the development of PM. The relationship between LAMA1 gene and patho- logical myopia is still waiting for the further proof.