Waalen Jill, Felitti Vincent, Gelbart Terri, Ho Ngoc J, Beutler Ernest
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
Mayo Clin Proc. 2002 Jun;77(6):522-30. doi: 10.4065/77.6.522.
To determine the prevalence of hemochromatosis-related symptoms in homozygotes for the HFE mutation C282Y compared with controls without HFE mutations identified through a large screening program of subjects attending a health appraisal center.
Presence of symptoms commonly associated with clinical hemochromatosis was ascertained by self-report on a written questionnaire among C282Y homozygotes and HFE wild-type subjects of white or Hispanic ethnicity identified from screening 41,599 adult subjects between March 1999 and August 2001. A subset of C282Y homozygotes and wild-type subjects identified from 12,756 subjects attending the center in the final year of the study completed a standardized double-blind interview with a physician regarding the presence, duration, and severity of a larger set of symptoms. Prevalence of symptoms among C282Y homozygotes and wild-type controls ascertained by written questionnaire and interview were compared by chi2 analysis or Fisher exact test. Symptoms among subjects with other combinations of the C282Y and H63D HFE mutations were also assessed by questionnaire.
The 124 C282Y homozygotes who filled out the written questionnaire and the 17 C282Y homozygotes who completed the physician double-blind interview reported no significantly higher rates of arthritis or joint pain, abdominal pain, arrhythmias, darkening of skin, or other symptoms traditionally associated with hemochromatosis compared with the 22,429 wild-type controls who filled out the written questionnaire and 29 wild-type controls who completed the double-blind interview. The only symptom reported more frequently by C282Y homozygotes was loss of body hair, reported by 5 C282Y/C282Y female subjects compared with 1 wild-type male subject (P=.02) in the physician interview. Symptoms among subjects with other HFE genotypes were similar to symptoms of wild-type subjects.
Results of this study indicate that many of the symptoms associated with hemochromatosis are common among HFE wild types and that clinical penetrance of the C282Y/C282Y genotype in regard to these symptoms is low.
通过对参加健康评估中心大型筛查项目的受试者进行大规模筛查，确定与HFE突变C282Y纯合子相比，无HFE突变的对照组中血色素沉着症相关症状的患病率。
通过对1999年3月至2001年8月期间筛查的41599名成年受试者中确定的C282Y纯合子以及白种或西班牙裔HFE野生型受试者进行书面问卷调查，以确定与临床血色素沉着症通常相关的症状。在研究最后一年从12756名到该中心就诊的受试者中确定的一部分C282Y纯合子和野生型受试者，就更多种类症状的存在、持续时间和严重程度与一名医生完成了标准化双盲访谈。通过卡方分析或费舍尔精确检验比较通过书面问卷和访谈确定的C282Y纯合子和野生型对照组中症状的患病率。还通过问卷评估了具有C282Y和H63D HFE突变其他组合的受试者中的症状。
与填写书面问卷的22429名野生型对照组以及完成双盲访谈的29名野生型对照组相比，填写书面问卷的124名C282Y纯合子和完成医生双盲访谈的17名C282Y纯合子报告的关节炎或关节痛、腹痛、心律失常、皮肤变黑或其他传统上与血色素沉着症相关的症状发生率没有显著更高。C282Y纯合子报告更频繁的唯一症状是体毛脱落，在医生访谈中，5名C282Y/C282Y女性受试者报告有此症状，而1名野生型男性受试者报告有此症状（P=0.02）。具有其他HFE基因型的受试者中的症状与野生型受试者的症状相似。
本研究结果表明，许多与血色素沉着症相关的症状在HFE野生型中很常见，并且C282Y/C282Y基因型对于这些症状的临床外显率较低。
