Barton James C, Chen Wen-Pin, Emond Mary J, Phatak Pradyumna D, Subramaniam V Nathan, Adams Paul C, Gurrin Lyle C, Anderson Gregory J, Ramm Grant A, Powell Lawrie W, Allen Katrina J, Phillips John D, Parker Charles J, McLaren Gordon D, McLaren Christine E
Southern Iron Disorders Center, Birmingham, AL, 35209, USA; Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Chao Family Comprehensive Cancer Center, Irvine, CA 92697, USA.
Blood Cells Mol Dis. 2017 Mar;63:15-20. doi: 10.1016/j.bcmd.2016.11.009. Epub 2016 Nov 12.
GNPAT p.D519G positivity is significantly increased in HFE p.C282Y homozygotes with markedly increased iron stores. We sought to determine associations of p.D519G and iron-related variables with iron stores in p.C282Y homozygotes.
We defined markedly increased iron stores as serum ferritin >2247pmol/L (>1000μg/L) and either hepatic iron >236μmol/g dry weight or iron >10g by induction phlebotomy (men and women). We defined normal or mildly elevated iron stores as serum ferritin <674.1pmol/L (<300μg/L) or either age≥40y with iron ≤2.5g iron by induction phlebotomy or age≥50y with ≤3.0g iron by induction phlebotomy (men only). We compared participant subgroups using univariate methods. Using multivariable logistic regression, we evaluated associations of markedly increased iron stores with these variables: age; iron supplement use (dichotomous); whole blood units donated; erythrocyte units received as transfusion; daily alcohol consumption, g; and p.D519G positivity (heterozygosity or homozygosity).
The mean age of 56 participants (94.6% men) was 55±10 (SD) y; 41 had markedly increased iron stores. Prevalences of swollen/tender 2nd/3rd metacarpophalangeal joints and elevated aspartate or alanine aminotransferase were significantly greater in participants with markedly increased iron stores. Only participants with markedly increased iron stores had cirrhosis. In multivariable analyses, p.D519G positivity was the only exposure variable significantly associated with markedly increased iron stores (odds ratio 9.9, 95% CI [1.6, 60.3], p=0.0126).
GNPAT p.D519G is strongly associated with markedly increased iron stores in p.C282Y homozygotes after correction for age, iron-related variables, and alcohol consumption.
在铁储存显著增加的HFE基因p.C282Y纯合子中，GNPAT基因p.D519G阳性率显著升高。我们试图确定p.D519G及铁相关变量与p.C282Y纯合子中铁储存的关联。
我们将铁储存显著增加定义为血清铁蛋白>2247pmol/L（>1000μg/L），且通过诱导放血法（男性和女性）测得肝铁>236μmol/g干重或铁>10g。我们将铁储存正常或轻度升高定义为血清铁蛋白<674.1pmol/L（<300μg/L），或年龄≥40岁且通过诱导放血法测得铁≤2.5g（男性），或年龄≥50岁且通过诱导放血法测得铁≤3.0g（仅男性）。我们使用单变量方法比较参与者亚组。使用多变量逻辑回归，我们评估铁储存显著增加与以下变量的关联：年龄；铁补充剂使用情况（二分变量）；捐献的全血单位数；作为输血接受的红细胞单位数；每日酒精摄入量（克）；以及p.D519G阳性（杂合性或纯合性）。
56名参与者（94.6%为男性）的平均年龄为55±10（标准差）岁；41人铁储存显著增加。在铁储存显著增加的参与者中，第二/三掌指关节肿胀/压痛以及天冬氨酸或丙氨酸转氨酶升高的患病率显著更高。只有铁储存显著增加的参与者患有肝硬化。在多变量分析中，p.D519G阳性是唯一与铁储存显著增加显著相关的暴露变量（比值比9.9，95%置信区间[1.6，60.3]，p = 0.0126）。
在校正年龄、铁相关变量和酒精摄入量后，GNPAT基因p.D519G与p.C282Y纯合子中铁储存显著增加密切相关。
