Analysis of the single genotypes of the three
LOXL1 common sequence variants (rs2165241T>C, rs1048661G>T, and rs3825942G>A) in the PEX and PEXG patients from Germany and Italy, as well as respective control subjects are shown in
Table 2where differences in genotype distribution among patients and control subjects were detected in both populations. Strong association with the risk allele of each individual SNP (rs2165241T, rs1048661G, and rs3825942G) was observed in German samples of both PEX and PEXG, similar to that found in the Icelandic and Swedish samples
12 with ORs between 2.49 and 3.26
(Table 3) . Similar results were obtained in the Italian group with ORs ranging from 2.09 to 3.71. No ORs could be calculated for rs3825942 (G153D), as all Italian patients analyzed were homozygous for the G allele at this SNP. Overall, allele frequencies in both populations in cases and control subjects were quite similar to those previously reported in Scandinavian patients.
12 Thus, we combined the results from German and Italian patients groups and observed a maximum OR = 2.43 (
P = 2.90 × 10
−19) for allele G of SNP rs1048661 and a maximum OR = 4.87 (
P = 8.22 × 10
−23) for allele G of SNP rs3825942
(Table 3) . It is also to note that, in both populations, the individual ORs of each single allele were similar for PEXG and PEX syndrome
(Table 3)showing that the risk of glaucoma is due to the presence of PEX.
Haplotype analysis derived from allelic combination of the two nonsynonymous SNPs, rs1048661 and rs3825942, which are in complete linkage disequilibrium (D′ = 1) detected only three of the four possible haplotypes (G-G; T-G, and G-A), both in the German and Italian groups
(Table 4) . Similar to the data from the Scandinavian population
12 the haplotype (T-A) was not seen in our samples. Among the three haplotypes observed (G-G, T-G, and G-A), the main common haplotype in the population (G-G) is the only overrepresented one in all patient groups of the two population and independent of the occurrence of glaucoma
(Table 4) . Thus, we calculated a combined OR for PEX and PEXG in German and Italian patients (OR = 3.58;
P = 5.21 × 10
−43). Moreover, two copies of the high-risk haplotype (G-G homozygosity) were identified in 66.1% of our total patients’ cohorts compared with 27.3% of our complete control subjects (OR = 5.2, 95% CI = 3.99–6.78;
P = 1.7 × 10
−37). Our results clearly confirm the genetic association previously seen in Scandinavian populations.