Keoki Williams

The association between leptin and left ventricular hypertrophy: a population-based cross-sectional study

Background and objectives Plasma leptin levels have been shown to be an independent risk factor for cardiovascular disease. Leptin has been shown to have sympathetic and vascular effects, and may increase cardiovascular risk through increased blood pressure, left ventricular hypertrophy, or atherosclerotic mechanisms. This study examines whether leptin levels, independent of body mass and insulin resistance, are a risk factor for hypertension and left ventricular hypertrophy. Methods and participants A population-based, cross-sectional sample of 410 adults from rural Spain was studied. The correlations between plasma leptin levels and left ventricular mass index, sum of wall thicknesses, and blood pressure were calculated. Multiple linear regression analysis was used to adjust for other cardiovascular risk factors. Results After adjusting for age, body mass index, systolic blood pressure, sex, and insulin resistance, leptin was inversely associated with left ventricular mass index (β = −0.20, P < 0.01). Leptin was also inversely related to the sum of wall thicknesses; however, this association did not reach statistical significance (β = −0.12, P = 0.063). Leptin was not statistically associated with blood pressure after adjusting for body mass index. Conclusions The results do not support the hypothesis that leptin increases cardiovascular risk by increasing left ventricular mass index or blood pressure. Other mechanisms, related to atherosclerosis, could explain the increased risk of cardiovascular diseases observed with high leptin levels.

Breastfeeding associated with higher lung function in African American youths with asthma.

ABSTRACT Objective: In the United States, Puerto Ricans and African Americans have lower prevalence of breastfeeding and worse clinical outcomes for asthma compared with other racial/ethnic groups. We hypothesize that the history of breastfeeding is associated with increased forced expiratory volume in 1 second (FEV1) % predicted and reduced asthma exacerbations in Latino and African American youths with asthma. Methods: As part of the Genes-environments & Admixture in Latino Americans (GALA II) Study and the Study of African Americans, asthma, Genes & Environments (SAGE II), we conducted case-only analyses in children and adolescents aged 8–21 years with asthma from four different racial/ethnic groups: African Americans (n = 426), Mexican Americans (n = 424), mixed/other Latinos (n = 255), and Puerto Ricans (n = 629). We investigated the association between any breastfeeding in infancy and FEV1% predicted using multivariable linear regression; Poisson regression was used to determine the association between breastfeeding and asthma exacerbations. Results: Prevalence of breastfeeding was lower in African Americans (59.4%) and Puerto Ricans (54.9%) compared to Mexican Americans (76.2%) and mixed/other Latinos (66.9%; p < 0.001). After adjusting for covariates, breastfeeding was associated with a 3.58% point increase in FEV1% predicted (p = 0.01) and a 21% reduction in asthma exacerbations (p = 0.03) in African Americans only. Conclusion: Breastfeeding was associated with higher FEV1% predicted in asthma and reduced number of asthma exacerbations in African American youths, calling attention to continued support for breastfeeding.

Genome-wide association study of asthma in individuals of African ancestry reveals novel asthma susceptibility loci

BACKGROUND Asthma is a complex disease with striking disparities across racial and ethnic groups, which may be partly attributable to genetic factors. One of the main goals of the Consortium on Asthma among African-ancestry Populations in the Americas (CAAPA) is to discover genes conferring risk to asthma in populations of African descent. METHODS We performed a genome-wide meta-analysis of asthma across 11 CAAPA datasets (4,827 asthma cases and 5,397 controls), genotyped on the African Diaspora Power Chip (ADPC) and including existing GWAS array data. The genotype data were imputed up to a whole genome sequence reference panel from n=880 African ancestry individuals for a total of 61,904,576 SNPs. Statistical models appropriate to each study design were used to test for association, and results were combined using the weighted Z-score method. We also used admixture mapping as a complementary approach to identify loci involved in asthma pathogenesis in subjects of African ancestry. RESULTS SNPs rs787160 and rs17834780 on chromosome 2q22.3 were significantly associated with asthma (p=6.57 × 10−9 and 2.97 × 10−8, respectively). These SNPs lie in the intergenic region between the Rho GTPase Activating Protein 15 (ARHGAP15) and Glycosyltransferase Like Domain Containing 1 (GTDC1) genes. Four low frequency variants on chromosome 1q21.3, which may be involved in the “atopic march” and which are not polymorphic in Europeans, also showed evidence for association with asthma (1.18 ×10−6 ≤ p ≤ 3.06 ×10−6). SNP rs11264909 on chromosome 1q23.1, close to a region previously identified by the EVE asthma meta-analysis as having a putative African ancestry specific effect, only showed differences in counts in subjects homozygous for alleles of African ancestry. Admixture mapping also identified a significantly associated region on chromosome 6q23.2, which includes the Transcription Factor 21 (TCF21) gene, previously shown to be differentially expressed in bronchial tissues of asthmatics and non-asthmatics. CONCLUSIONS We have identified a number of novel asthma association signals warranting further investigation.

Genomic Loci Evaluation with Albuminuria in New-Onset Insulin Dependent Diabetic Patients

Background: Extensive data supports the genetic underpinnings of diabetes and recent studies implicate several genetic loci associated with renal insufficiency and albuminuria. Moreover, albuminuria in diabetic patients is an important risk marker for atherosclerotic disease as well as cardiomyopathy. The purpose of this study was to identify genetic determinants of albuminuria in a diabetic patient population at the time of insulin initiation. Methods: Study population included type 2 diabetic subjects at the time of initiation of insulin in an observational cohort who donated saliva samples for DNA extraction. Urine albumin to creatinine ratio (UACR) and HbA1c levels at baseline were collected and analyzed for association with genotype (N=128). Results: Although none of the SNPs met statistical significance after Bonferroni adjustment, two regions showed near-significant associations with UACR; one on chromosome 1 (p=8.66 E-07) and one on chromosome 12 (p=9.82 E-07). Conclusions: In this small study of newly insulin-dependent diabetics we identified two genomic regions possibly associated with albuminuria. These loci are good candidates for further investigation into the moderators of cardiovascular disease in diabetics. Larger confirmatory studies are needed.