The Association of African Ancestry and elevated creatinine in the Coronary Artery Risk Development in Young Adults (CARDIA) Study

Department of Medicine, University of California San Francisco, USA.
American Journal of Nephrology (Impact Factor: 2.65). 12/2009; 31(3):202-8. DOI: 10.1159/000268955
Source: PubMed

ABSTRACT Whether genetic factors account for differences in early kidney disease among blacks in a young healthy population is not well known. We evaluated the association of self-reported race and genetic African ancestry with elevated creatinine (> or =1.3 mg/dl for men, > or =1.1 mg/dl for women) among 3,113 black and white participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study, ages 38-50 years. We estimated individual African ancestry using 42 ancestry informative markers. Blacks were more likely to have elevated creatinine than whites, and this effect was more pronounced in men: adjusted odds ratio (AOR) for black versus white men = 7.03, 4.15-11.91; AOR for women = 2.40, 1.15-5.02. Higher African ancestry was independently associated with elevated creatinine among black men (AOR = 1.53,1.08-2.16 per SD increase in African ancestry), but not women. A graded increase in odds of elevated creatinine by African Ancestry was observed among black men compared with white men: AOR = 4.27 (2.26-10.06) for black men with 40-70% African ancestry; AOR = 8.09 (4.19-15.61) for black men with 70-80% African ancestry; AOR = 9.05 (4.81-17.02) for black men with >80% African ancestry. Genetic factors common to African ancestry may be associated with increased risk of early kidney dysfunction in a young, healthy population, particularly among black men.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Large epidemiologic studies examining differences in cardiovascular disease (CVD) risk factor profiles between European Americans and African Americans have exclusively used self-identified race (SIR) to classify individuals. Recent genetic epidemiology studies of some CVD risk factors have suggested that biogeographic ancestry (BGA) may be a better predictor of CVD risk than SIR. This hypothesis was investigated in 464 African Americans and 771 European Americans enrolled in the Heart Strategies Concentrating on Risk Evaluation (Heart SCORE) Study in March and April 2010. Individual West African and European BGA were ascertained by means of a panel of 1,595 genetic ancestry informative markers. Individual BGA varied significantly among African Americans and to a lesser extent among European Americans. In the total cohort, BGA was not found to be a better predictor of CVD risk factors than SIR. Both measures predicted differences in the presence of the metabolic syndrome, waist circumference, triglycerides, body mass index, very low density lipoprotein cholesterol, lipoprotein A, and systolic and diastolic blood pressure between European Americans and African Americans. These results suggest that for most nongenetic cardiovascular epidemiology studies, SIR is sufficient for predicting CVD risk factor differences between European Americans and African Americans. However, higher body mass index and diastolic blood pressure were significantly associated with West African BGA among African Americans, suggesting that BGA should be considered in genetic cardiovascular epidemiology studies carried out among African Americans.
    American journal of epidemiology 07/2012; 176(2):146-55. DOI:10.1093/aje/kwr518 · 4.98 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Compared with European Americans, African Americans (AAs) exhibit lower levels of the cardio-metabolically protective adiponectin even after accounting for adiposity measures. Because few studies have examined in AA the association between adiponectin and genetic admixture, a dense panel of ancestry informative markers (AIMs) was used to estimate the individual proportions of European ancestry (PEA) for the AAs enrolled in a large community-based cohort, the Jackson Heart Study (JHS). We tested the hypothesis that plasma adiponectin and PEA are directly associated and assessed the interaction with a series of cardio-metabolic risk factors. Methods: Plasma specimens from 1439 JHS participants were analyzed by ELISA for adiponectin levels. Using pseudo-ancestral population genotype data from the HapMap Consortium, PEA was estimated with a panel of up to 1447 genome-wide preselected AIMs by a maximum likelihood approach. Interaction assessment, stepwise linear and cubic multivariable-adjusted regression models were used to analyze the cross-sectional association between adiponectin and PEA. Results: Among the study participants (62% women; mean age 48 ± 12 years), the median (interquartile range) of PEA was 15.8 (9.3)%. Body mass index (BMI) (p = 0.04) and insulin resistance (p = 0.0001) modified the association between adiponectin and PEA. Adiponectin was directly and linearly associated with PEA (β = 0.62 ± 0.28, p = 0.03) among non-obese (n = 673) and insulin sensitive participants (n = 1141; β = 0.74 ± 0.23, p = 0.001), but not among those obese or with insulin resistance. No threshold point effect was detected for non-obese participants. Conclusions: In a large AA population, the individual proportion of European ancestry was linearly and directly associated with plasma adiponectin among non-obese and non insulin-resistant participants, pointing to the interaction of genetic and metabolic factors influencing adiponectin levels.
    Frontiers in Genetics 02/2014; 5:22. DOI:10.3389/fgene.2014.00022
  • [Show abstract] [Hide abstract]
    ABSTRACT: Worldwide, an estimated 200 million people have chronic kidney disease (CKD). In the United States, African Americans (AAs) have a four-fold excess risk of CKD compared to non-Hispanic white people and globally, people in the low-to-middle income countries of Asia and Sub-Saharan Africa have the highest rates of CKD. Annually, more than 500,000 individuals develop end-stage renal disease (or CKD stage 5) in Sub-Saharan Africa alone and the vast majority of these patients suffer premature mortality. The health care costs and economic burden of CKD are huge and not sustainable even in advanced Western countries. A recent discovery on the role of Apolipoprotein 1 (APOL1) G1 and G2 renal risk variants in AAs has a huge potential to unravel the etiology of CKD in both AA and other black populations. Under the National Institutes of Health (NIH)-sponsored Human Heredity and Health in Africa (H3Africa) initiative, a large prospective genetic study of CKD is being conducted in 8000 participants in four African countries (Ethiopia, Ghana, Kenya, and Nigeria; for a total population of 320 million). This and other basic research studies in the United States could potentially shed great insight into the genetics and biologic mechanisms involved in the excess predilection of Africans and AAs to CKD.
    Transactions of the American Clinical and Climatological Association 01/2014; 125:229-46.
Show more