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J. Mok, Y.-H. Kim, S.-H. Chung, J.-M. Park, C.-K. Joo; Variants of the Loc387715/arms2 and Htra1 Genes Are Associated With Higher Risk of Korean Patients With Exudative Age Related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3441.
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© ARVO (1962-2015); The Authors (2016-present)
To determine the possibility of LOC387715/ARMS2 and high-temperature requirement A-1 (HTRA1) as major susceptibility genes for Korean patients with exudative AMD, we investigated the association of variants in LOC387715/ARMS2 and HTRA1 genes.
Total genomic DNAs were extracted from buccal swab samples of 112 unrelated patients with exudative AMD visited the Department of Ophthalmology at the Catholic University Medical Center. Polymerase chain reaction - restriction fragment length polymorphism and direct sequencing were used to screen genetic variations in LOC387715 and HTRA1 genes. Age matched 230 control individuals from Korea Centers for Disease Control and Prevention with no history of AMD were also enrolled.
In this study, we investigated 8 SNPs for LOC387715/ARMS2 and 7 SNPs of HTRA1; rs10490923 (R3H), rs2736911 (R38X) and rs10490924 (A69S) in exon 1, rs10664316, rs3750848 and rs3750846 in intron 1 and rs4752698 and rs3672602 in 3’UTR region of LOC387715/ARMS2, and -625 G>A (rs11200638), -602 G>A, -502 C>T and -487 T>C (rs2672598) in promoter region, two synonymous substitutions in exon 1 (rs1049331 and rs2293870) and rs714816 in intron 3 of HTRA1. Among them, rs273691, rs10490924, rs10664316, rs3750848 and rs3750846 of LOC387715/ARMS2 and rs11200638, -502 C>T, rs2672598, rs1049331 and rs2293870 of HTRA1 were significantly different between patients and control groups. In particularly, rs1049331 (A34A) and rs2293870 (G36G) with two synonymous substitutions in HTRA1 are the most significant associated SNPs with a high odds ratio (O.R.) of 12.9 (95% CI: 7.264<<23.109), respectively. In the haplotype analysis of SNPs in both genes, we identified two risk haplotype blocks: rs10490924/rs3750848/rs3750846/rs11200638/-502C>T/rs2672598 and rs1049331/rs2293870. One risk haplotype block across the LOC387715/ARMS2 and HTRA1, TACGCC, significantly predisposes to AMD (p<0.0001, O.R. = 12.6, 95% CI: 4.517<<34.973). And TT for rs1049331/rs2293870 was also found to be significantly different between patients and control groups (p<0.0001, O.R. = 4.81, 95%CI: 3.309<<6.996).
The present study suggests that the genetic variants in LOC387715/ARMS2 and HTRA1, in particularly rs10490924 of LOC387715/ARMS2 and rs1049331 and rs2293870 of HTRA1, are associated with a higher risk of exudative AMD in Korean.
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