Genes as Biomarkers in Korean Age-related Macular Degeneration (AMD) Patients : CFH and LOC387715

Abstract

Purpose: : : To investigate the sensitive gene variations of CFH and LOC387715 in Korean AMD patients and determine their possibility as biomarkers for genetic factors predisposing to AMD.

Methods: : 114 exudative AMD patients with choroidal neovascularization and 240 normal healthy subjects participated in the study. Sensitivity was determined by performing PCR-RFLP and direct sequencing for 7 SNPs from CFH at 1q31.3 (Y402H, exons 2, 7, and introns 4, 9, 11, 14) and exon 1 and 5 SNPs in the 3’ UTR region from LOC387715 at 10q26.13.

Results: : Analysis of CFH gene showed the frequency of the CT type rs1061170 from exon 9 (Y402H) was significantly higher in AMD patients (P=0.049, OR=1.79). The frequencies of heterozygous genotypes in rs1329424 (intron 4), rs1061147 (exon 7), and rs10801555 (intron 9) were also higher than the control group, although statistically not significant. The remaining SNPs showed no significant difference. Haplotype analysis did not reveal any significant difference either. Analysis of LOC387715 gene showed the frequencies of the CC genotype from exon 1 (rs2736911; P<0.0001, OR=3.21) and TT genotype from rs10490924 (A69S; P=0.001, OR=12.45) were both higher in the AMD group. Haplotype analysis showed that CT haplotype from rs2736911-rs10490924 was significantly higher in the AMD group (P<0.0001, O.R.=4.85).

Conclusions: : Korean AMD patients in our study showed significant difference in CFH and LOC387715 from the control group. The difference was more pronounced in the SNPs that included A69S in the LOC38775 gene. LOC387715 is known as a secondary sensitive gene for CFH, and seems to be more important as a genetic factor predisposing to AMD in Koreans than CFH, which is known as a primary sensitive gene for AMD. Therefore LOC387715 seems possible as a biomarker for Korean AMD patients.

Keywords: age-related macular degeneration • genetics • candidate gene analysis