Subsequently, if needed, significant results will be subjected to multiple curve estimation procedure [66] and/ or multivariate analysis according to data characteristics and the results of the univariate analyses. The genetic data will be analyzed using χ 2 test for the Hardy-Weinberg equilibrium of alleles at the individual loci. The association between genotypes and clinical data will be tested with χ 2 -or Fisher test and then with logistic regression or analysis of co-variance, as appropriate [67] . All statistical analyses will be performed by the project coordinators, who have a long experience and formal training in biostatistics.