Background:
Major chronic diseases such as cardiovascular disease, renal dysfunction and metabolic syndrome are having excessive impact on African Americans with higher prevalence rates, mortality and morbidity. But, relatively very few studies have been conducted among populations of African ancestry to evaluate the disease burden and etiology. This proposed study was built upon seven large, multigenerational families of African descent, residing on the island of Tobago, to investigate the genetic impact on major chronic diseases, and to evaluate the association of novel biochemical markers with subclinical cardiovascular measurements.
Methods:
Lipid profiles, subclinical cardiovascular measurements and renal function biomarkers were measured in 402 Afro-Caribbean individuals, aged 18 to 103 years, from 7 large, multi-generation pedigrees (average family size: 50; range: 19 to 96; 3535 relative pairs). Estimated GFR was calculated using the Modification of Diet in Renal Disease Study (MDRD) formula for standardized serum creatinine. Heritability (h2) of cardio-metabolic renal traits was estimated employing maximum likelihood methods using SOLAR (Sequential Oligogenic Linkage Analysis Routines). Multivariate regression analysis was performed to assess the association between renal function biomarkers and the subclinical cardiovascular measures, incorporating the effects of the relatedness of family members.
Results:
We determined that, among these Afro-Caribbeans of Tobago, renal function and metabolic syndrome related traits are all heritable phenotypes. The additive genetic effects accounted for 20-30% of the residual variation of several kidney function related traits. The heritability of each metabolic component ranged from 21% for large waist circumference to 46% for HDL-cholesterol (P<0.05). Using the National Cholesterol Education Program Expert Panel (NCEP) and Treatment of High Blood Cholesterol in Adults (Adult Treatment panel III) (ATP III) definition, 18.6% (23.3% women and 11.8% men) of the participants had metabolic syndrome.
As a novel renal function biomarker, Cystatin C has heritability of 0.32 ± 0.1 (P<0.0001), after adjusting for age, gender, hypertension, triglyceride and insulin level. Not only does cystatin C indicate renal function, but it was also significantly associated with ABI (P=0.02) and PWV (P=0.04) in this Afro-Caribbean population. Serum creatinine, microalbuminuria and eGFR were not found to be related to subclinical cardiovascular disease.
Public Health Significance:
This work was the first to estimate the heritability of renal function biomarkers and metabolic syndrome related traits among an African ancestry population living in the Caribbean. The significant finding of the association between serum Cystatin C level and subclinical cardiovascular disease suggest a promising biomarker for both renal function and cardiovascular disease. If this result is confirmed, Cystatin C could be a useful prognostic tool in this high risk population.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-11272010-140302 |
| Date | 31 January 2011 |
| Creators | Li, Hu |
| Contributors | M.Michael Barmada, Clareann Bunker, Joseph Zmuda, Lewis Kuller, Candace Kammerer |
| Publisher | University of Pittsburgh |
| Source Sets | University of Pittsburgh |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.pitt.edu/ETD/available/etd-11272010-140302/ |
| Rights | restricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to University of Pittsburgh or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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