Date of Award

12-2008

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Program

Nursing

Research Advisor

Ann K. Cashion, PhD

Committee

Patricia Cowan, PhD Carolyn Driscoll, PhD Carolyn Graff, PhD Jane Hankins, MD, MS

Abstract

This study explored the relationship of a dinucleotide repeat polymorphism in the intron of the CRP gene and serum CRP levels as independent risk factors for end-organ dysfunction (mild vs. severe) in adults with sickle cell disease. The pathogenesis of secondary complications of sickle cell disease is complex and poorly understood. Predicting the severity of these complications could assist in therapeutic decision-making.

The study measured serum CRP levels and the number of CA intron repeats located on the CRP gene in 29 adults (31.74 ± 11.54 years) with sickle cell disease The hemoglobin genotypes were distributed as Hgb SS 48.6% (17 of n = 29), Hgb SC 20.0% (7 of n = 29), Sβ° 10.3% (3 of n = 29), and Sβ+ 6.9% (2 of n = 29). The sample was categorized as mild (n = 9) no end-organ dysfunction vs. severe (n = 21) documented end-organ dysfunction. The severe group was sub-categorized by specific organ dysfunctions, 9 with pulmonary hypertension, 6 with renal dysfunction and 6 with cerebral vascular accident. Examination of serum CRP levels found no significant association with severe end-stage organ dysfunction. There was no significant association between serum CRP level and the polymorphism. However, a significant negative correlation (rho = -0.401, p = 0.031) was found between glomerular filtration rates and CAhigh repeats (≥17).

Previous studies have found an association of genetic variations in the CRP gene polymorphism to serum CRP levels. While this pilot study found no evidence of this association, the findings provide some rationale for further investigation of the repeat polymorphism in the CRP gene and its association with renal end-organ dysfunction.

DOI

10.21007/etd.cghs.2008.0052

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