HFE p.S65C (rs1800730) in Europe: A Geographic Study

HFE (homeostatic iron regulator) p.S65C (rs1800730) is associated with European ancestry, although there is no comprehensive geographic study of p.S65C in Europe.

We tabulated published p.S65C genotypes in European population/control cohorts, depicted allele frequency ranges in a map, and computed correlations of p.S65C allele frequencies with latitudes and longitudes of cohort recruitment sites.

We identified 44 cohorts from 24 of the 44 countries of Europe. These 24 countries comprise ~62.9% of Europe's population. There were 233,528 subjects, including 38 HFE p.S65C homozygotes (~1 in 6145 subjects) and 4347 p.S65C heterozygotes (~1 in 54 subjects). Genotypes in 42 cohorts (95.5%) were consistent with Hardy-Weinberg equilibrium. The median allele frequency was 0.0129 (range 0-0.0350). p.S65C was not reported in Bulgaria, although the allele frequency in non-Bulgarian cohorts did not differ significantly (0/200 vs. 4423/462,432, respectively; p = 0.2728). Allele frequency ranges (means) were 0-0.0100 (0.0087), 0.0101-0.0200 (0.0146), and ≥0.0201 (0.0253) in 7, 14, and 3 respective aggregate country cohorts (p < 0.0001, all mean comparisons). The seven countries with low-range frequencies extend from north to south (Estonia to Italy). The three countries with high-range frequencies are east of ~14.1° E (western-most border of Poland). Correlations of allele frequencies with latitudes and longitudes in 44 cohorts were not significant (p = 0.1745 and 0.6031, respectively).

We conclude that the median HFE p.S65C allele frequency in Europe is 0.0129, allele frequencies differ between some countries, and there is no linear north-to-south or west-to-east allele frequency gradient.