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  • Title: Longer survival associated with HLA-A*03, B*14 among 212 hemochromatosis probands with HFE C282Y homozygosity and HLA-A and -B typing and haplotyping.
    Author: Barton JC, Barton JC, Acton RT.
    Journal: Eur J Haematol; 2010 Nov; 85(5):439-47. PubMed ID: 20722701.
    Abstract:
    BACKGROUND: Human leukocyte antigen (HLA) haplotypes may influence iron phenotypes in patients with HFE hemochromatosis and could affect survival. METHODS: We tabulated general characteristics of HLA-A and -B types and haplotypes of HFE C282Y/C282Y probands diagnosed in medical care and analyzed these data to identify HLA survival modifiers. RESULTS: There were 212 probands (130 men, 82 women). Mean follow-up was 12.0 ± 6.4 yr (0.1-41.2 yr; 34 deaths). HLA-A*03 was more prevalent in men (76.9% vs. 61.0% women; P = 0.0129); 35.4% of men and 29.3% of women had A*03, B*07; and 7.7% of men and 8.5% of women had A*03, B*14. Twenty-three probands had cirrhosis; none had A*03, B*14. Positivity for A*03 or A*03, B*07 was not a significant predictor or modifier of survival. In multiple regression analyses, A*03, B*14 predicted longer survival (P = 0.0004). Kaplan-Meier analysis confirmed longer survival in probands with A*03, B*14 (P = 0.0199, log-rank test). After excluding the 23 non-A*03, B*14 probands with cirrhosis, survival of probands with A*03, B*14 was still greater than that of probands without A*03, B*14 (P = 0.0254; log-rank test). Twenty-four years after diagnosis, cumulative survival of probands with and without A*03, B*14 was 100% and 58%, respectively. The percentage of deaths due to iron overload was lower in probands with A*03, B*14 (0% vs. 21.9%; P = 0.0392). CONCLUSIONS: In hemochromatosis probands with HFE C282Y/C282Y, survival was longer in those with HLA-A*03, B*14. Earlier age at diagnosis and less severe iron overload in probands with A*03, B*14 could explain this difference.
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