Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
Southern Iron Disorders Center, Birmingham, Alabama, United States of America.
PLoS One. 2022 Jul 27;17(7):e0271973. doi: 10.1371/journal.pone.0271973. eCollection 2022.
Screening program participants with iron overload (IO) phenotypes without HFE p.C282Y/p.C282Y are incompletely characterized.
We studied white participants who had IO phenotypes without p.C282Y/p.C282Y in post-screening clinical examinations (CE). We defined IO phenotypes as a) elevated serum ferritin (SF) and transferrin saturation (TS) at screening and CE, and b) absence of IO treatment, anemia, transfusion >10 units, alcohol intake >30 g/d, hepatitis B or C, and pregnancy. We defined IO-related disease as elevated alanine or aspartate aminotransferase (ALT/AST) or swelling/tenderness of 2nd/3rd metacarpophalangeal (MCP) joints. All participants had HFE p.C282Y and p.H63D genotyping.
There were 32 men and 26 women (mean age 54±16 y). Median food/supplemental iron intakes were 14.3/0.0 mg/d. Relative risks of HFE genotypes were 12.9 (p.C282Y/p.H63D), 3.0 (p.H63D/p.H63D), 1.9 (p.C282Y/wt), 0.9 (p.H63D/wt), and 0.5 (wt/wt) compared to 42,640 white screening participants without IO phenotypes or p.C282Y/p.C282Y. Regression on SF revealed positive associations: MCV (p = 0.0006; β coefficient = 0.4531); swelling/tenderness of MCP joints (p = 0.0033; β = 0.3455); and p.H63D/wt (p = 0.0015; β = 0.4146). IO-related disease (18 elevated ALT/AST, one swelling/tenderness of MCP joints) occurred in 19 participants (7 men, 12 women). Median MCV was higher in participants with IO-related disease (97 fL vs. 94 fL; p = 0.0007). Logistic regression on IO-related disease revealed a significant association with diabetes (p = 0.0416; odds ratio 18.9 (95% confidence interval 1.0, 341.1)).
In the present 58 screening program participants who had IO phenotypes without HFE p.C282Y/p.C282Y, relative risks of HFE genotypes p.C282Y/p.H63D, p.H63D/p.H63D, and p.C282Y/wt were significantly higher than in 42,640 white screening participants with neither IO phenotypes nor p.C282Y/p.C282Y. SF was significantly associated with MCV, swelling/tenderness of 2nd/3rd MCP joints, and p.H63D/wt. IO-related disease was significantly associated with MCV and diabetes.
未经 HFE p.C282Y/p.C282Y 筛查的铁过载（IO）表型参与者的特征并不完全清楚。
我们研究了在筛查后临床检查（CE）中具有 IO 表型而无 p.C282Y/p.C282Y 的白种人参与者。我们将 IO 表型定义为：a）在筛查和 CE 时血清铁蛋白（SF）和转铁蛋白饱和度（TS）升高，b）无 IO 治疗、贫血、输血>10 单位、酒精摄入量>30g/d、乙型肝炎或丙型肝炎和妊娠。我们将 IO 相关疾病定义为丙氨酸或天冬氨酸转氨酶（ALT/AST）升高或第 2/3 掌指关节（MCP）肿胀/压痛。所有参与者均进行了 HFE p.C282Y 和 p.H63D 基因分型。
有 32 名男性和 26 名女性（平均年龄 54±16 岁）。中位食物/补充铁摄入量分别为 14.3/0.0mg/d。HFE 基因型的相对风险分别为 12.9（p.C282Y/p.H63D）、3.0（p.H63D/p.H63D）、1.9（p.C282Y/wt）、0.9（p.H63D/wt）和 0.5（wt/wt），与 42640 名无 IO 表型或 p.C282Y/p.C282Y 的白人筛查参与者相比。SF 的回归显示出阳性关联：MCV（p=0.0006；β系数=0.4531）；MCP 关节肿胀/压痛（p=0.0033；β=0.3455）；和 p.H63D/wt（p=0.0015；β=0.4146）。18 名参与者（7 名男性，12 名女性）发生了与 IO 相关的疾病（18 名 ALT/AST 升高，1 名 MCP 关节肿胀/压痛）。患有 IO 相关疾病的参与者的 MCV 中位数更高（97fL 与 94fL；p=0.0007）。IO 相关疾病的逻辑回归显示与糖尿病有显著关联（p=0.0416；比值比 18.9（95%置信区间 1.0，341.1））。
在目前 58 名具有 HFE p.C282Y/p.C282Y 无 IO 表型的筛查参与者中，HFE 基因型 p.C282Y/p.H63D、p.H63D/p.H63D 和 p.C282Y/wt 的相对风险明显高于 42640 名无 IO 表型和 p.C282Y/p.C282Y 的白人筛查参与者。SF 与 MCV、2/3 MCP 关节肿胀/压痛和 p.H63D/wt 显著相关。IO 相关疾病与 MCV 和糖尿病显著相关。
