In relation to the study by Fuse and associates performed on a Japanese population, we investigated the presence of the allelic and genotypic association in Italian subjects affected by exudative age-related macular degeneration (AMD). We analyzed the single nucleotide polymorphism (SNP) rs1048661 (Arg141Leu) in the lysyl oxidase–like 1 ( LOXL1 ) gene mapped on 15q24.1. We typed 974 Italian subjects divided into 3 different groups: 342 patients with diagnosis of AMD, 198 subjects clinically evaluated without any form of macular degeneration (healthy control group), and 434 subjects not clinically evaluated (general population). Inclusion criteria of subjects in the different classes have been previously described. Genotyping of the SNP rs1048661 was obtained by digestion with SmaI enzyme, as described elsewhere. Statistical analyses were performed by a standard 2 × 2 table and Fisher exact tests. We compared allele and genotype frequencies of the affected subjects with those obtained from the clinically unexamined control subjects (n = 198) and separately with those from the general population (n = 434), obtaining the following results: G allele of rs1048661 showed a percentage frequency of 0.68 in cases, 0.70 in controls, and 0.69 in the general population while the frequency of T allele was 0.32 in cases, 0.30 in controls, and 0.31 in the general population. Finally, we failed to reveal evidence of allele association between the polymorphism rs1048661 and AMD in both controls and general population ( P = .509 and P = .579, respectively). As expected, the genotypic association confirmed the absence of association ( P = .325 and P = .185) and excluded any deviation from Hardy-Weinberg equilibrium.
Our results suggest that rs1048661 is not implicated in the development of AMD in the Italian population in spite of a very good statistical power to replicate the reported strong associations. The discrepancy between the data from Japanese and Italian populations could be explained by the presence of genetic heterogeneity. Indeed, it is well known that the association and the risk of a given variant can differ substantially between populations because of different genetic and environmental factors. On the other hand, Fuse and associates analyzed a small number of samples, making possible the generation of false-positive results. We believe that this marker should be typed in other independent cohorts from Asia and Europe to better define the role of LOXL1 in the susceptibility to AMD.