HLA genes and surnames show a similar genetic structure in Lombardy: does this reflect part of the history of the region?

Lombardy, in northern Italy, is the most populated and industrialized Italian region. We attempt to study its genetic structure with two independent sets of data: HLA allele frequencies and surnames. According to our results, it is plausible to deduce that ancient history, more than genetic isolation and drift, may have contributed to the present genetic structure of Lombardy. The hypothesis seems to be confirmed by the results of the cluster analysis of the 11 provinces of the region, which was performed using two different types of markers. Both genes and surnames show approximately the same structure. Not only Celts but also ancient Ligurians (and Etruscans) probably shaped the region into the present three clusters in which the 11 provinces appear to be genetically structured. In particular, an ancient historic, archaeological, and linguistic boundary, along the Adda River, seems to be preserved in present-day Lombardy's population structure.

High prevalence of a screening-detected, HFE-unrelated, mild idiopathic iron overload in Northern Italy.

BACKGROUND AND OBJECTIVES: In Italy, typical HFE mutations account for only 64% of the cases with overt hereditary hemochromatosis (HH), and a common HFE-unrelated disease was hypothesized. DESIGN AND METHODS: One thousand and fifty potential blood donors were screened by iron tests, C282Y and H63D HFE mutation analysis in a region in North Italy. Subjects with repeated fasting transferrin saturation of 45% or more and no secondary iron overload were defined as probands with idiopathic iron overload. To assess the inheritance of iron overload, relatives of probands were screened. RESULTS: The overall frequency of probands with idiopathic iron overload was 3.43% (95% confidence interval, 2.32 to 4.52). Of these, 8.4% had genotypes associated with HH (compound heterozygous for H63D/C282Y or homozygous for H63D HFE mutations), and 91.6% had atypical genotypes: 47.2% were heterozygous for C282Y or H63D HFE mutations, and 44.4% had wild type/wild type genotype. A family history of iron overload was proven in 33.3% of probands with atypical genotypes (1.04% of the overall population). Pedigree analysis excluded linkage of heterozygous HFE mutations with iron overload (cumulative lod score 2.41) and documented a recessive non-HLA-linked locus accounting for iron overload in wild type/wild type genotypes. None of the probands had clinical signs of iron accumulation; in males, serum ferritin positively correlated with age (r=0.63, p<0.01), and the regression model predicted a serum ferritin of 700 ng/mL at the age of 58. INTERPRETATION AND CONCLUSIONS: In Northern Italy an HFE-unrelated, mild idiopathic iron overload is highly prevalent. A recessive locus accounts for iron overload in at least 1.04% of the overall population.