Sickle Cell Trait and Risk for Common Diseases: Evidence from the UK Biobank |
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| Institution: | 1. Program for Personalized Cancer Care, Evanston, Ill;2. Department of Surgery, NorthShore University HealthSystem, Evanston, Ill;3. Department of Surgery, University of Chicago Pritzker School of Medicine, Ill;4. Department of Medicine, NorthShore University HealthSystem, Evanston, Ill;5. Department of Medicine, University of Chicago Pritzker School of Medicine, Ill;6. Department of Pediatrics, NorthShore University HealthSystem, Evanston, Ill;7. Department of Pediatrics, University of Chicago Pritzker School of Medicine, Ill;1. Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Md;2. Division of Nephrology and Hypertension, Henry Ford Hospital, Detroit, Mich;3. Division of Nephrology and Hypertension, MedStar Georgetown University Hospital, Washington, DC;4. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Md;5. Welch Center for Prevention, Epidemiology, and Clinical Research, Baltimore, Md;6. Nephrology Center of Maryland, Baltimore;7. Division of Nephrology, Department of Medicine, University of California, San Francisco;1. Laboratory of Anatomy, Medical School, Democritus University of Thrace, Alexandroupolis, Greece;2. Medical School, National and Kapodistrian University of Athens, Athens, Greece;3. Computed Tomography and MRI Department, Sismanogleion General Hospital, Athens, Greece;4. Clinic of Plastic Surgery, Medical School, Democritus University of Thrace, Alexandroupolis, Greece;1. Department of Medicine, New York Medical College, Valhalla, NY;2. Director of Clinical Ethics, Columbia University Medical Center/New York Presbyterian Hospital, New York, NY;1. Walter Reed National Military Medical Center, Department of Medicine, Bethesda, Md;2. Uniformed Services University of the Health Sciences, Bethesda, Md |
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| Abstract: | BackgroundSickle 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.MethodsStudy 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).ResultsAmong 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.ConclusionsSickle cell trait is significantly associated with increased risk for diabetes and diabetes-related complications/comorbidities. |
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