Gurrin Lyle C, Bertalli Nadine A, Dalton Gregory W, Osborne Nicholas J, Constantine Clare C, McLaren Christine E, English Dallas R, Gertig Dorota M, Delatycki Martin B, Nicoll Amanda J, Southey Melissa C, Hopper John L, Giles Graham G, Anderson Gregory J, Olynyk John K, Powell Lawrie W, Allen Katrina J
Centre for MEGA Epidemiology, School Population Health, University of Melbourne, Victoria, Australia.
Hepatology. 2009 Jul;50(1):94-101. doi: 10.1002/hep.22972.
The risk of hemochromatosis-related morbidity is unknown among HFE compound heterozygotes (C282Y/H63D). We used a prospective population-based cohort study to estimate the prevalence of elevated iron indices and hemochromatosis-related morbidity for compound heterozygotes. In all, 31,192 subjects of northern European descent were genotyped for HFE C282Y and H63D. An HFE-genotype stratified random sample of 1,438 subjects, followed for an average of 12 years to a mean age of 65 years, completed questionnaires and gave blood. Clinical examinations were blinded to HFE genotype. A total of 180 (84 males) clinically examined C282Y/H63D participants were compared with 330 (149 males) controls with neither HFE mutation; 132 (65 males) and 270 (122 males), respectively, had serum iron measures at both timepoints. Mean serum ferritin (SF) and transferrin saturation (TS) were significantly greater for male and female compound heterozygotes than for wild-types at baseline and follow-up (all P < 0.02) except for females who were premenopausal at baseline, where SF was similar in both genotype groups. For subjects with serum measures from both baseline and follow-up, mean SF and TS levels did not change significantly for men or for postmenopausal women, but for premenopausal women SF levels increased from 43 to 109 microg/L for compound heterozygotes and from 35 to 64 microg/L for wild-types (both P < 0.001). Male and female compound heterozygotes had a similar prevalence of hemochromatosis-related morbidity to wild-types. One of 82 males and zero of 95 females had documented iron overload-related disease.
For male compound heterozygotes, mean iron indices do not change during middle age but for female compound heterozygotes menopause results in increased mean SF. Although compound heterozygotes might maintain elevated iron indices during middle age, documented iron overload-related disease is rare.
HFE复合杂合子（C282Y/H63D）发生血色素沉着症相关发病的风险尚不清楚。我们采用一项基于人群的前瞻性队列研究来估计复合杂合子铁指标升高及血色素沉着症相关发病的患病率。总共对31192名北欧血统受试者进行了HFE C282Y和H63D基因分型。从HFE基因型分层的1438名受试者随机样本中，平均随访12年至平均年龄65岁，完成问卷调查并献血。临床检查对HFE基因型不知情。将总共180名（84名男性）接受临床检查的C282Y/H63D参与者与330名（149名男性）无HFE突变的对照者进行比较；分别有132名（65名男性）和270名（122名男性）在两个时间点均进行了血清铁检测。在基线和随访时，男性和女性复合杂合子的平均血清铁蛋白（SF）和转铁蛋白饱和度（TS）均显著高于野生型（所有P<0.02），但基线时处于绝经前的女性除外，这两个基因型组的SF相似。对于在基线和随访时均有血清检测结果的受试者，男性和绝经后女性的平均SF和TS水平无显著变化，但对于绝经前女性，复合杂合子的SF水平从43微克/升增至109微克/升，野生型从35微克/升增至64微克/升（均P<0.001）。男性和女性复合杂合子发生血色素沉着症相关发病的患病率与野生型相似。82名男性中有1名、95名女性中无1名有记录在案的铁过载相关疾病。
对于男性复合杂合子，中年期间平均铁指标无变化，但对于女性复合杂合子，绝经导致平均SF升高。尽管复合杂合子在中年期间可能维持较高的铁指标，但有记录在案的铁过载相关疾病很少见。
