Hemochromatosis genotypes and risk of iron overload--a meta-analysis.
OBJECTIVE
The incomplete phenotypic penetrance of high iron Fe genotypes in relation to hemochromatosis poses a practical problem in the interpretation of the genotyping results by clinicians. We carried out meta-analyses of the associations between hemochromatosis genotypes C282Y/C282Y, C282Y/H63D, C282Y/wild-type, H63D/H63D, H63D/wild-type, versus wild-type/wild-type and iron overload, both provisional (elevated serum iron markers) and documented (elevated serum iron markers associated with evidence of iron excess based on liver biopsy and/or quantitative phlebotomy).


METHODS
After reviewing 3572 article titles and evaluating 92 articles in detail, odds ratios were pooled from 43 study populations (9986 cases and 25,492 controls) using a random-effects model.


RESULTS
Homozygosity for either variant or compound heterozygosity was associated with both provisional and documented iron overload. Single heterozygosity conferred no risk for elevated hepatic iron index and/or mobilizable iron by quantitative phlebotomy. In patients with clinical hereditary hemochromatosis, no evidence of provisional and documented iron overload with transferrin saturation (TS) values greater than 55% was evidenced for C282Y and H63D single heterozygotes whereas documented iron overload including TS of 45% to 50% was weakly associated with C282Y/wild-type genotype; H63D/H63D genotype was not associated with documented iron overload in patients with TS values of 45% to 50%.


CONCLUSIONS
The results, mainly from case-control studies, cannot necessarily be extrapolated to the general population.
Neghina
Adriana Maria
AM
Biochemistry Department, Victor Babes University of Medicine and Pharmacy, Timisoara, Romania. aneghina@umft.ro
Anghel
Andrei
A
D005838:Genotype; D006432:Hemochromatosis / Q000235:genetics*; D000071020:Hemochromatosis Protein; D006579:Heterozygote; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D019190:Iron Overload / Q000453:epidemiology*; D008565:Membrane Proteins / Q000235:genetics*; D020125:Mutation, Missense; D016017:Odds Ratio; D012306:Risk
C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins