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.
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.
Barton
James C
JC
Southern Iron Disorders Center, Birmingham, AL, USA. ironmd@dnamail.com
Barton
J Clayborn
JC
Acton
Ronald T
RT
D000328:Adult; D000368:Aged; D005260:Female; D015234:HLA-A Antigens / Q000032:analysis*; D015791:HLA-A3 Antigen; D015235:HLA-B Antigens / Q000032:analysis*; D059909:HLA-B14 Antigen; D006239:Haplotypes; D006432:Hemochromatosis / Q000235:genetics / Q000276:immunology* / Q000401:mortality*; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006650:Histocompatibility Testing; D006720:Homozygote; D006801:Humans; D019190:Iron Overload; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D020125:Mutation, Missense; D012737:Sex Factors; D015996:Survival Rate
C103673:HFE protein, human; D015234:HLA-A Antigens; C487960:HLA-A*03 antigen; D015791:HLA-A3 Antigen; D015235:HLA-B Antigens; D059909:HLA-B14 Antigen; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins