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African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P

BACKGROUND Chronic kidney disease (CKD) and arterial stiffness are associated with increased cardiovascular morbidity and mortality. Inflammation is proposed to have a role in the development of arterial stiffness, and CKD is recognized as a proinflammatory state. Arterial stiffness is increased in CKD, and cross-sectional data has suggested a link between increased inflammatory markers in CKD and higher measures of arterial stiffness. However, no large scale investigations have examined the impact of inflammation on the progression of arterial stiffness in CKD. METHODS We performed baseline assessments of 5 inflammatory markers in 3,939 participants from the chronic renal insufficiency cohort (CRIC), along with serial measurements of arterial stiffness at 0, 2, and 4 years of follow-up. RESULTS A total of 2,933 participants completed each of the follow-up stiffness measures. In cross-sectional analysis at enrollment, significant associations with at least 2 measures of stiffness were observed for fibrinogen, interleukin-6, high-sensitivity C-reactive protein, proteinuria, and composite inflammation score after adjustment for confounders. In longitudinal analyses, there were few meaningful correlations between baseline levels of inflammation and changes in metrics of arterial stiffness over time. CONCLUSION In a large cohort of CKD participants, we observed multiple significant correlations between initial markers of inflammation and metrics of arterial stiffness, but baseline inflammation did not predict changes in arterial stiffness over time. While well-described biologic mechanisms provide the basis for our understanding of the cross-sectional results, continued efforts to design longitudinal studies are necessary to fully elucidate the relationship between chronic inflammation and arterial stiffening. [ABSTRACT FROM AUTHOR]

Background Micro RNAs (mi RNAs) are noncoding RNA molecules that play important roles in the pathogenesis of various kidney diseases. We investigated whether patients with minimal change disease ( MCD) and focal segmental glomerulosclerosis ( FSGS) have distinct circulating and urinary mi RNA expression profiles that could lead to potential development of noninvasive biomarkers of the disease. Materials and methods Exosome mi RNAs were extracted from plasma and urine samples of patients with primary FSGS ( n = 16) or MCD ( n = 5) and healthy controls ( n = 5). Differences in mi RNA abundance were examined using Affymetrix GeneChip mi RNA 3.0 arrays. QRT- PCR was used to validate the findings from the array. Results Comparison analysis of FSGS versus MCD revealed 126 and 155 differentially expressed mi RNAs in plasma and in urine, respectively. Only 38 of these mi RNAs were previously cited, whereas the remaining mi RNAs have not been described. Comparison analysis showed that a significant number of mi RNAs were downregulated in both plasma and urine samples of patients with FSGS compared to those with MCD. Plasma levels of miR-30b, miR-30c, miR-34b, miR-34c and miR-342 and urine levels of mir-1225-5p were upregulated in patients with MCD compared to patients with FSGS and controls ( P < 0·001). Urinary levels of mir-1915 and miR-663 were downregulated in patients with FSGS compared to MCD and controls ( P < 0·001), whereas the urinary levels of miR-155 were upregulated in patients with FSGS when compared to patients with MCD and controls ( P < 0·005). Conclusions Patients with FSGS and MCD have a unique circulating and urinary mi RNA profile. The diagnostic and prognostic potential of mi RNAs in FSGS and MCD warrants further studies. [ABSTRACT FROM AUTHOR]

Objective The race-specific association of inflammation with adiposity and muscle mass in subjects with chronic kidney disease (CKD) was examined. Methods Plasma concentration of interleukin (IL)−1β, IL-1 receptor antagonist (IL-1RA), IL-6, IL-10, tumor necrosis factor (TNF)-α, TGF-β, high-sensitivity C-reactive protein (hs-CRP), fibrinogen, and serum albumin was measured in 3,939 Chronic Renal Insufficiency Cohort study participants. Bioelectric impedance analysis was used to determine body fat mass (BFM) and fat-free mass (FFM). Results Plasma levels of hs-CRP, fibrinogen, IL-1RA, IL-6, and TNF-α increased and serum albumin decreased across the quartiles of body mass index. In multivariable analysis, BFM and FFM were positively associated with hs-CRP, fibrinogen, IL-1β, IL-1RA, and IL-6. One standard deviation (SD) increase in BFM and FFM was associated with 0.36 (95% confidence interval [CI] = 0.33, 0.39) and 0.26 (95% CI = 0.22, 0.30) SD increase in log-transformed hs-CRP, respectively ( P < 0.001). Race stratified analysis showed that the association between biomarkers and BFM and FFM differed by race, with Caucasians, demonstrating a stronger association with markers of inflammation than African Americans. Conclusions BFA and FFM are positively associated with markers of inflammation in patients with CKD. Race stratified analysis showed that Caucasians have a stronger association with markers of inflammation compared to African Americans. [ABSTRACT FROM AUTHOR]