Haptoglobin phenotype 2-2 overrepresentation in Cys282Tyr hemochromatotic patients

Background/Aims: Patients with genotypic Cys282Tyr homozygous hemochromatosis differ largely in phenotypic presentation. The HFE mutation on itself does not explain the different manifestations of hemochromatosis. We hypothesized that the genetic haptoglobin (Hp) polymorphism, because of its effect on iron metabolism, could be a modifying factor that influences the clinical presentation of hereditary hemochromatosis. Methods: In 167 Cys282Tyr homozygous hemochromatotic patients, the frequencies of Hp types (1-1, 2-1 and 2-2) and alleles (Hp1, Hp2) were compared with those in 918 healthy subjects. Clinical and laboratory indices of iron overload were incorporated in the analysis. Results: The Hp 2-2 type was overrepresented in the patient group (P<0.01). Male patients carrying Hp 2-2 had higher serum iron (P=0.003) and ferritin levels (P=0.03) than those with a Hp 1-1 or 2-1 type. The amount of iron removed with phlebotomy was also higher in Hp 2-2 patients (P=0.03). Conclusions: The Hp 2-2 type is overrepresented among Cys282Tyr homozygous hemochromatotic patients. At diagnosis, iron overload was more pronounced in male patients carrying Hp 2-2. Our data suggest that Hp polymorphism affects iron metabolism in hereditary hemochromatosis.