Polymorphisms in ARMS2 ( LOC387715 ) and LOXL1 Genes in the Japanese With Age-Related Macular Degeneration

• Published in: American journal of ophthalmology 2011-03, Vol.151 (3), p.550-556.e1
• Main Authors: Fuse, Nobuo, Mengkegale, Mingge, Miyazawa, Akiko, Abe, Toshiaki, Nakazawa, Toru, Wakusawa, Ryosuke, Nishida, Kohji
• Format: Article
• Language: English
• Subjects: Aged; Amino Acid Oxidoreductases - genetics; Asian Continental Ancestry Group - genetics; Biological and medical sciences; Choroid Diseases - genetics; Female; Gene Frequency; Genotype; Geographic Atrophy - genetics; Humans; Macular Degeneration - genetics; Male; Medical sciences; Miscellaneous; Ophthalmology; Peripheral Vascular Diseases - genetics; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Proteins - genetics; Retinopathies; Sequence Analysis, DNA; Wet Macular Degeneration - genetics
• ISSN: 0002-9394; 1879-1891
• DOI: 10.1016/j.ajo.2010.08.048

Purpose To determine whether polymorphisms in the ARMS2 ( LOC387715 ) gene and the lysyl oxidase–like 1 ( LOXL1 ) gene are associated with age-related macular degeneration (AMD) in Japanese patients. Design Clinically relevant laboratory investigation. Methods Forty-one unrelated Japanese subjects with dry AMD, 50 subjects with exudative (wet) AMD, and 60 subjects with polypoidal choroidal vasculopathy (PCV) were studied. The single nucleotide polymorphisms (SNPs), p.Ala69Ser of the ARMS2 gene and p.Arg141Leu of the LOXL1 gene, were amplified by polymerase chain reaction, directly sequenced, and genotyped. Results For the ARMS2 gene, the genotype frequency of the p.Ala69Ser single nucleotide polymorphism in eyes with dry AMD was not significantly different from that in the controls ( P = .04), but the frequency was significantly higher in the exudative AMD group ( P = 3.1 × 10−8 ) and PCV group ( P = 6.9 × 10−3 ). For the LOXL1 gene, the genotype frequency of the p.Arg141Leu single nucleotide polymorphism was not statistically higher in the dry AMD and PCV groups than in the control group (dry AMD, P = .05; PCV, P = .16), but was statistically higher in the exudative AMD group ( P = 6.8 × 10−3 ). Regression analyses showed significant associations between the ARMS2 gene and LOXL1 gene in patients with exudative AMD. Conclusions The p.Ala69Ser polymorphism of the ARMS2 gene is strongly associated with exudative AMD and PCV and is associated marginally with dry AMD. The polymorphisms in the LOXL1 gene did not predispose the individual to dry AMD and PCV. These findings suggest that there is a significant association between the ARMS2 gene and LOXL1 gene in exudative AMD.