镰状细胞特征与常见疾病风险：来自英国生物库的证据。

Sickle Cell Trait and Risk for Common Diseases: Evidence from the UK Biobank.

机构信息

Program for Personalized Cancer Care, Evanston, Ill.

Program for Personalized Cancer Care, Evanston, Ill; Department of Surgery, NorthShore University HealthSystem, Evanston, Ill; Department of Surgery, University of Chicago Pritzker School of Medicine, Ill.

出版信息

Am J Med. 2022 Aug;135(8):e279-e287. doi: 10.1016/j.amjmed.2022.03.024. Epub 2022 Apr 22.

DOI:10.1016/j.amjmed.2022.03.024

PMID:35461807

Abstract

BACKGROUND

Sickle cell trait is typically considered benign. Although evidence remains inconsistent, recent studies suggest that it is associated with several common diseases. We systematically assessed associations of sickle cell trait with reported diseases in a large population-based cohort.

METHODS

Study subjects were self-reported Blacks from the UK Biobank (UKB), a United Kingdom population-based cohort of subjects aged 40-69 years at recruitment in the United Kingdom. Sickle cell status was based on the International Classification of Diseases, Tenth Revision (ICD-10) or mutations in the HBB gene. Diagnoses of diseases were obtained from ICD-10 and self-reports. Associations of sickle cell trait and diseases were tested using logistic regression, adjusting for age at recruitment, sex, and genetic background (top 10 principal components).

RESULTS

Among the 8019 Blacks in the UKB, 699 (8.72%) were sickle cell trait carriers; the rate was significantly higher in females (9.74%) than males (7.48%), P = .0005. Sickle cell trait was under-diagnosed; most heterozygous hemoglobin subunit beta (HBB) gene Glu6Val carriers did not have a sickle cell trait ICD-10 record. Compared with non-sickle cell trait, sickle cell trait carriers had significantly increased risk for type 2 diabetes; odds ratio 1.38; 95% confidence interval, 1.12-1.68; P = .002. Sickle cell trait was also significantly associated with increased risk for renal diseases (rhabdomyolysis, end-stage renal disease, chronic kidney disease, renal papillary necrosis) and vascular diseases (hypertension, retinopathy, non-ischemic stroke), P < .05. While most of these diseases are complications/comorbidities of diabetes, their associations with sickle cell trait remained significant after adjusting for diabetes. Association with end-stage renal disease was stronger in subjects without diabetes, odds ratio 6.45; 95% confidence interval, 1.93-19.61; P = .001.

CONCLUSIONS

Sickle cell trait is significantly associated with increased risk for diabetes and diabetes-related complications/comorbidities.

摘要

背景

镰状细胞特质通常被认为是良性的。尽管证据仍不一致，但最近的研究表明，它与几种常见疾病有关。我们在一个大型基于人群的队列中系统地评估了镰状细胞特质与报告疾病的关联。

方法

研究对象是来自英国生物银行（UKB）的自报黑人，这是一个英国基于人群的队列，招募时年龄在 40-69 岁。镰状细胞状态基于国际疾病分类，第十版（ICD-10）或 HBB 基因的突变。疾病的诊断来自 ICD-10 和自我报告。使用逻辑回归测试镰状细胞特质与疾病的关联，调整招募时的年龄、性别和遗传背景（前 10 个主成分）。

结果

在 UKB 的 8019 名黑人中，有 699 名（8.72%）是镰状细胞特质携带者；女性（9.74%）的发生率明显高于男性（7.48%），P=0.0005。镰状细胞特质被低估诊断；大多数杂合血红蛋白亚单位β（HBB）基因 Glu6Val 携带者没有镰状细胞特质 ICD-10 记录。与非镰状细胞特质相比，镰状细胞特质携带者患 2 型糖尿病的风险显著增加；优势比 1.38；95%置信区间，1.12-1.68；P=0.002。镰状细胞特质也与肾脏疾病（横纹肌溶解症、终末期肾病、慢性肾脏病、肾乳头坏死）和血管疾病（高血压、视网膜病变、非缺血性中风）的风险增加显著相关，P<0.05。虽然这些疾病大多数是糖尿病的并发症/合并症，但在调整糖尿病后，它们与镰状细胞特质的关联仍然显著。在没有糖尿病的患者中，与终末期肾病的关联更强，优势比 6.45；95%置信区间，1.93-19.61；P=0.001。