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Genetic predictors for cardiovascular disease in hispanics.

ABSTRACT: A less favorable cardiovascular risk factor profile but paradoxically lower cardiovascular morbidity and mortality have been observed in Hispanics--a pattern often referred to as the Hispanic paradox. It has been proposed that the specific genetic susceptibility of this admixed population and gene-environment interactions may partly explain the paradox. During the past few years, there have been major advances in the identification of genetic risk factors using genome-wide association studies (GWAS) for cardiovascular disease, especially in Caucasians. However, no GWAS of cardiovascular disease have been reported in Hispanics. In the Costa Rican Heart Study, we reported both the consistency and disparity of genetic effects on risk of coronary heart disease (CHD) between Hispanics and other ethnic groups. We demonstrated that the improvement in the identified genetic markers on discrimination of CHD in Hispanics was modest. Future genetic research on Hispanics should consider the diversity in genetic structure, lifestyle, and socioeconomics among various subpopulations and comprehensively evaluate potential gene-environment interactions in relation to cardiovascular risk.

SUBMITTER: Qi L

PROVIDER: S-EPMC3326380 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

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Genetic predictors for cardiovascular disease in hispanics.

Qi Lu L Campos Hannia H

Trends in cardiovascular medicine 20110101 1

A less favorable cardiovascular risk factor profile but paradoxically lower cardiovascular morbidity and mortality have been observed in Hispanics--a pattern often referred to as the Hispanic paradox. It has been proposed that the specific genetic susceptibility of this admixed population and gene-environment interactions may partly explain the paradox. During the past few years, there have been major advances in the identification of genetic risk factors using genome-wide association studies (G ...[more]

PMID: 22498015

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Project description:Cerebrospinal fluid (CSF) levels of amyloid-β 42 (Aβ42) and tau have been evaluated as endophenotypes in Alzheimer's disease (AD) genetic studies. Although there are sex differences in AD risk, sex differences have not been evaluated in genetic studies of AD endophenotypes. We performed sex-stratified and sex interaction genetic analyses of CSF biomarkers to identify sex-specific associations. Data came from a previous genome-wide association study (GWAS) of CSF Aβ42 and tau (1527 males, 1509 females). We evaluated sex interactions at previous loci, performed sex-stratified GWAS to identify sex-specific associations, and evaluated sex interactions at sex-specific GWAS loci. We then evaluated sex-specific associations between prefrontal cortex (PFC) gene expression at relevant loci and autopsy measures of plaques and tangles using data from the Religious Orders Study and Rush Memory and Aging Project. In Aβ42, we observed sex interactions at one previous and one novel locus: rs316341 within SERPINB1 (p = 0.04) and rs13115400 near LINC00290 (p = 0.002). These loci showed stronger associations among females (β = - 0.03, p = 4.25 × 10-8; β = 0.03, p = 3.97 × 10-8) than males (β = - 0.02, p = 0.009; β = 0.01, p = 0.20). Higher levels of expression of SERPINB1, SERPINB6, and SERPINB9 in PFC was associated with higher levels of amyloidosis among females (corrected p values < 0.02) but not males (p > 0.38). In total tau, we observed a sex interaction at a previous locus, rs1393060 proximal to GMNC (p = 0.004), driven by a stronger association among females (β = 0.05, p = 4.57 × 10-10) compared to males (β = 0.02, p = 0.03). There was also a sex-specific association between rs1393060 and tangle density at autopsy (pfemale = 0.047; pmale = 0.96), and higher levels of expression of two genes within this locus were associated with lower tangle density among females (OSTN p = 0.006; CLDN16 p = 0.002) but not males (p ≥ 0.32). Results suggest a female-specific role for SERPINB1 in amyloidosis and for OSTN and CLDN16 in tau pathology. Sex-specific genetic analyses may improve understanding of AD's genetic architecture.

Project description:IntroductionProteomic profiling of end-stage renal disease (ESRD) patients could lead to improved risk prediction and novel insights into cardiovascular disease mechanisms. Plasma levels of 92 cardiovascular disease-associated proteins were assessed by proximity extension assay (Proseek Multiplex CVD-1, Olink Bioscience, Uppsala, Sweden) in a discovery cohort of dialysis patients, the Mapping of Inflammatory Markers in Chronic Kidney disease cohort [MIMICK; n?=?183, 55% women, mean age 63 years, 46 cardiovascular deaths during follow-up (mean 43 months)]. Significant results were replicated in the incident and prevalent hemodialysis arm of the Salford Kidney Study [SKS dialysis study, n?=?186, 73% women, mean age 62 years, 45 cardiovascular deaths during follow-up (mean 12 months)], and in the CKD5-LD-RTxcohort with assessments of coronary artery calcium (CAC)-score by cardiac computed tomography (n?=?89, 37% women, mean age 46 years).ResultsIn age and sex-adjusted Cox regression in MIMICK, 11 plasma proteins were nominally associated with cardiovascular mortality (in order of significance: Kidney injury molecule-1 (KIM-1), Matrix metalloproteinase-7, Tumour necrosis factor receptor 2, Interleukin-6, Matrix metalloproteinase-1, Brain-natriuretic peptide, ST2 protein, Hepatocyte growth factor, TNF-related apoptosis inducing ligand receptor-2, Spondin-1, and Fibroblast growth factor 25). Only plasma KIM-1 was associated with cardiovascular mortality after correction for multiple testing, but also after adjustment for dialysis vintage, cardiovascular risk factors and inflammation (hazard ratio) per standard deviation (SD) increase 1.84, 95% CI 1.26-2.69, p?=?0.002. Addition of KIM-1, or nine of the most informative proteins to an established risk-score (modified AROii CVM-score) improved discrimination of cardiovascular mortality risk from C?=?0.777 to C?=?0.799 and C?=?0.823, respectively. In the SKS dialysis study, KIM-1 predicted cardiovascular mortality in age and sex adjusted models (hazard ratio per SD increase 1.45, 95% CI 1.03-2.05, p?=?0.034) and higher KIM-1 was associated with higher CACscores in the CKD5-LD-RTx-cohort.ConclusionsOur proteomics approach identified plasma KIM-1 as a risk marker for cardiovascular mortality and coronary artery calcification in three independent ESRD-cohorts. The improved risk prediction for cardiovascular mortality by plasma proteomics merit further studies.

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Genetic predictors for cardiovascular disease in hispanics.

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Genetic predictors for cardiovascular disease in hispanics.

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