A Decreasing North-to-South Gradient of HFE p.C282Y (rs1800562) Allele Frequencies in Iberia: An Analysis of 33 Population/Control Cohorts

Background: We sought to analyze the geographic distribution of HFE p.C282Y (homeostatic iron regulator c.845G>A; rs1800562) allele frequencies in Iberia. Methods: We analyzed published population/control cohorts of 50 or more subjects in mainland Spain and mainland Portugal and determined whether or not the p.C282Y genotypes in each cohort deviated from Hardy-Weinberg equilibrium (HWE) proportions. We defined combined p.C282Y allele frequencies from Spain and Portugal as representative of Iberia. We computed linear regressions (Pearson’s correlations) of allele frequencies vs. latitudes and longitudes of cohort recruitment sites, defined significant regressions as allele frequency gradients, and mapped regional allele frequencies. Results: There were 33 Iberian cohorts: 24 Spanish (12,082 subjects; 10 autonomous communities) and 9 Portuguese (1024 subjects; five administrative regions). p.C282Y genotypes in one of 33 cohorts (3.0%) deviated significantly from HWE proportions. Aggregate allele frequency in Iberia was 0.0291 (762/26,212) [95% confidence interval: 0.0271, 0.0312]. The correlation of allele frequencies vs. latitudes in Iberia was significant (r33 = 0.4129; p = 0.0152). The correlation of allele frequencies vs. longitudes was not significant (r33 = -0.0118; p = 0.9552). The range of 15 regional allele frequencies in Iberia was 0.0068 (Murcia) to 0.5000 (Galicia). Frequencies were highest in regions adjacent to the north and northwest coasts (Cantabria, Galicia, Norte) and lowest in the south (Algarve, Murcia). Conclusions: There is a significant decreasing linear north-to-south gradient of HFE p.C282Y allele frequencies in Iberia. p.C282Y allele frequencies are highest in regions adjacent to the north and northwest coasts.