# A Decreasing North-to-South Gradient of HFE p.C282Y (rs1800562) Allele Frequencies in Iberia: An Analysis of 34 Population/Control Cohorts

## TL;DR

This study finds that a specific genetic variant linked to iron regulation is more common in northern Iberia and decreases toward the south.

## Contribution

The study identifies a significant north-to-south gradient in HFE p.C282Y allele frequencies across Iberia using 34 population cohorts.

## Key findings

- HFE p.C282Y allele frequencies show a significant correlation with latitude in Iberia.
- Allele frequencies are highest in northern regions like Galicia and lowest in southern regions like Murcia.
- Only 2.9% of cohorts showed significant deviation from Hardy-Weinberg equilibrium.

## Abstract

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 34 Iberian cohorts: 25 Spanish (12,297 subjects; 11 autonomous communities) and 9 Portuguese (1024 subjects; five administrative regions). p.C282Y genotypes in one of 34 cohorts (2.9%) deviated significantly from HWE proportions. Aggregate allele frequency in Iberia was 0.0292 (778/26,642) [95% confidence interval: 0.0272, 0.0313]. The correlation of allele frequencies with latitude in Iberia was significant (r34 = 0.4184; p = 0.0138). The correlation of allele frequencies with longitude was not significant (r34 = 0.0014; p = 0.9936). The range of 16 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.