Hereditary Hemochromatosis Associations with Frailty, Sarcopenia and Chronic Pain: Evidence from 200,975 Older UK Biobank Participants.
Hereditary Hemochromatosis Associations with Frailty, Sarcopenia and Chronic Pain: Evidence from 200,975 Older UK Biobank Participants.
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遗传性血色素沉着病与虚弱、肌肉减少症和慢性疼痛的关联：来自 200,975 名英国生物银行老年参与者的证据。
DOI：
10.1093/gerona/gly270
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发表时间：
2019
期刊：
影响因子：
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通讯作者：
Tamosauskaite J
中科院分区：
文献类型：
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作者：
Tamosauskaite J
背景铁是生命所必需的，但有助于氧化损伤。在北欧血统人群中，HFE基因C282 Y突变相对常见（0.3%-0.6%的罕见纯合子患病率），并与过度铁吸收、疲劳、糖尿病、关节炎和肝病相关，尤其是在男性中。铁过量可以预防或治疗，但诊断往往被延误或错过。数据少肌症，疼痛，和frailty.MethodsUsing 200,975英国生物银行志愿者年龄在60-70岁，我们测试了C282 Y纯合性与油炸脆弱，少肌症，慢性疼痛之间的关联，使用logistic回归调整年龄和技术遗传协变量。由于铁超载是渐进的（月经保护），我们包括具体的分析老年人（65-70岁）的女性和男性。Results 13012（0.65%）的参与者是C282 Y纯合子; 593人（0.62%）和719人（0.68%）。与常见的“野生型”基因型相比，C282 Y纯合子男性报告慢性疼痛（优势比[OR] 1.23：95%置信区间[CI] 1.05- 1.45，p = 0.01）和诊断风湿性多肌痛的可能性增加。他们也更可能患有肌肉减少症（OR 2.38：1.80- 3.13，p = 9.70 × 10−10）和虚弱（OR 2.01：1.45- 2.80，p = 3.41 × 10−05）。年龄在65-70岁之间的C282 Y纯合子女性（n= 312，0.7%）更容易虚弱（OR 1.73：1.05- 2.84，p = 0.032），并有慢性膝关节、髋关节和背部疼痛。结论HFEC 282 Y基因纯合性与老年人肌肉减少症、虚弱和慢性疼痛有关。鉴于治疗的可用性，遗传性血色病是精确医学方法改善晚年结局的有力候选者。
BackgroundIron is essential for life but contributes to oxidative damage. In Northern-European ancestry populations,HFEgene C282Y mutations are relatively common (0.3%–0.6% rare homozygote prevalence) and associated with excessive iron absorption, fatigue, diabetes, arthritis, and liver disease, especially in men. Iron excess can be prevented or treated but diagnosis is often delayed or missed. Data on sarcopenia, pain, and frailty are scarce.MethodsUsing 200,975 UK Biobank volunteers aged 60–70 years, we tested associations between C282Y homozygosity with Fried frailty, sarcopenia, and chronic pain using logistic regression adjusted for age and technical genetic covariates. As iron overload is progressive (with menstruation protective), we included specific analyses of older (65–70 years) females and males.ResultsOne thousand three hundred and twelve (0.65%) participants were C282Y homozygotes; 593 were men (0.62%) and 719 were women (0.68%). C282Y homozygote men had increased likelihoods of reporting chronic pain (odds ratio [OR] 1.23: 95% confidence interval [CI] 1.05–1.45,p= .01) and diagnoses of polymyalgia rheumatica, compared to common “wild-type” genotype. They were also more likely to have sarcopenia (OR 2.38: 1.80–3.13,p= 9.70 × 10−10) and frailty (OR 2.01: 1.45–2.80,p= 3.41 × 10−05). C282Y homozygote women (n= 312, 0.7%) aged 65–70 were more likely to be frail (OR 1.73: 1.05–2.84,p= .032) and have chronic knee, hip, and back pain. Overall, 1.50% of frail men and 1.51% of frail women in the 65–70 age group were C282Y homozygous.ConclusionsHFEC282Y homozygosity is associated with substantial excess sarcopenia, frailty, and chronic pain at older ages. Given the availability of treatment, hereditary hemochromatosis is a strong candidate for precision medicine approaches to improve outcomes in late life.