212 名携带 HFE C282Y 纯合子且进行了 HLA-A 和 -B 分型和单体型分析的血色病先证者中，HLA-A03、B14 与更长的生存期相关。

Longer survival associated with HLA-A03, B14 among 212 hemochromatosis probands with HFE C282Y homozygosity and HLA-A and -B typing and haplotyping.

机构信息

Southern Iron Disorders Center, Birmingham, AL, USA.

出版信息

Eur J Haematol. 2010 Nov;85(5):439-47. doi: 10.1111/j.1600-0609.2010.01511.x.

DOI:10.1111/j.1600-0609.2010.01511.x

PMID: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-A03 was more prevalent in men (76.9% vs. 61.0% women; P = 0.0129); 35.4% of men and 29.3% of women had A03, B07; and 7.7% of men and 8.5% of women had A03, B14. Twenty-three probands had cirrhosis; none had A03, B14. Positivity for A03 or A03, B07 was not a significant predictor or modifier of survival. In multiple regression analyses, A03, B14 predicted longer survival (P = 0.0004). Kaplan-Meier analysis confirmed longer survival in probands with A03, B14 (P = 0.0199, log-rank test). After excluding the 23 non-A03, B14 probands with cirrhosis, survival of probands with A03, B14 was still greater than that of probands without A03, B14 (P = 0.0254; log-rank test). Twenty-four years after diagnosis, cumulative survival of probands with and without A03, B14 was 100% and 58%, respectively. The percentage of deaths due to iron overload was lower in probands with A03, B14 (0% vs. 21.9%; P = 0.0392).

CONCLUSIONS

In hemochromatosis probands with HFE C282Y/C282Y, survival was longer in those with HLA-A03, B14. Earlier age at diagnosis and less severe iron overload in probands with A03, B14 could explain this difference.

摘要

背景

人类白细胞抗原（HLA）单倍型可能会影响 C282Y/C282Y 基因型遗传性血色病患者的铁表型，并可能影响生存。

方法

我们整理了在医疗保健中诊断的 HFE C282Y/C282Y 先证者的 HLA-A 和 -B 类型和单倍型的一般特征，并分析这些数据以确定 HLA 生存修饰因子。

结果

共有 212 名先证者（男 130 例，女 82 例）。平均随访 12.0±6.4 年（0.1-41.2 年；34 例死亡）。男性 HLA-A03 更为常见（76.9%比 61.0%女性；P=0.0129）；35.4%的男性和 29.3%的女性有 A03、B07；7.7%的男性和 8.5%的女性有 A03、B14。23 名先证者患有肝硬化；没有 A03、B14。A03 或 A03、B07 阳性不是生存的显著预测因子或修饰因子。在多元回归分析中，A03、B14 预测生存时间更长（P=0.0004）。Kaplan-Meier 分析证实 A03、B14 先证者生存时间更长（P=0.0199，对数秩检验）。排除 23 例非 A03、B14 肝硬化先证者后，A03、B14 先证者的生存仍优于无 A03、B14 先证者（P=0.0254；对数秩检验）。诊断后 24 年，A03、B14 先证者的累积生存率分别为 100%和 58%。A03、B14 先证者因铁过载导致的死亡百分比较低（0%比 21.9%；P=0.0392）。