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.
Keywords
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Article Info
Publication History
Published online: April 21, 2022
Footnotes
Funding: NorthShore University HealthSystem.
Conflicts of Interest: None for all authors.
Authorship: All authors had access to the data and contributed to writing this manuscript.
Identification
Copyright
© 2022 Elsevier Inc. All rights reserved.
