Genetics of Atherosclerosis Risk Factors in Mexican Americans

MacCluer, Jean W.; Stern, Michael P.; Almasy, Laura; Atwood, Larry A.; Blangero, John; Comuzzie, Anthony G.; Dyke, Bennett; Haffner, Steven M.; Henkel, Richard D.; Hixson, James E.; Kammerer, Candace M.; Mahaney, Michael C.; Mitchell, Braxton D.; Rainwater, David L.; Samollow, Paul B.; Sharp, R. Mark; VandeBerg, John L.; Williams, Jeff T.

doi:10.1111/j.1753-4887.1999.tb01790.x

Cited by 74 publications

(67 citation statements)

References 20 publications

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“…The SAFHS includes 1240 individuals from 42 extended families of Mexican Americans from San Antonio, TX, USA. 9,15,16 This study aims to quantify the relative contributions of genetic and environmental factors to the risk of developing CVD and participants were not ascertained owing to CVD status. Phenotypic assessment of cardiovascular risk factors has been performed, including serum levels of lipids, lipoproteins, glucose, hormones, adiposity, and blood pressure.…”

Section: Methodsmentioning

confidence: 99%

Identification of ACOX2 as a shared genetic risk factor for preeclampsia and cardiovascular disease

et al. 2011

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Preeclampsia (PE) is a serious complication of pregnancy, which is highly correlated with later life cardiovascular disease (CVD). Many risk factors are common for both diseases, but the contribution of shared genes remains to be determined. In this study, we used an integrative strategy to assess lipid traits as risk factors for PE and CVD by whole genome transcriptional profiling performed on Norwegian decidua basalis tissues (N¼95) from preeclamptic and normal pregnancies and on blood lymphocytes (N¼1240) from the San Antonio Family Heart Study (SAFHS). Among 222 genes that were differentially expressed (false discovery rate (FDR) P-value o0.05) between the PE, cases and controls, we found one gene, ACOX2 (acyl-coenzyme A oxidase 2, branched chain), that was downregulated in PE whose transcription was also inversely correlated with triglyceride levels (P¼5.6Â10 À7 ; FDR P-value¼0.0002) in SAFHS. We further report associations between SNPs in the ACOX2 gene and the transcription level (P-value¼0.0045) of the gene, as well as with triglyceride levels (P-value¼0.0051). ACOX2 is involved in bile acid production, a process that has been associated with both oxidative stress and regulation of triglyceride levels. Oxidative stress and increased triglyceride levels are known risk factors for CVD and both have also been associated with PE. Our results suggest that downregulation of ACOX2 is a shared risk factor for PE and CVD.

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Section: Methodsmentioning

confidence: 99%

Identification of ACOX2 as a shared genetic risk factor for preeclampsia and cardiovascular disease

et al. 2011

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“…The recruitment and ascertainment procedures used in the SAFHS have been described in details elsewhere ( 27,29,30 ). Briefl y, the study has now recruited signifi cant factors for each individual.…”

Section: Study Subjectsmentioning

confidence: 99%

“…For these analyses, we used data from the ongoing San Antonio Family Heart Study (SAFHS) in Mexican Americans ( 27 ). These data and samples provide an appropriate opportunity for the aforementioned investigation for the following reasons: i ) MS is very common in Mexican Americans ( 28 ); ii ) the SAFHS recruited 42 large and extended pedigrees that help delineate the potential contribution of genetics to MS ( 29,30 ); iii ) high-resolution plasma lipidomic studies have been conducted on a large number of SAFHS participants ( 15 ); and iv ) using these data, we have previously demonstrated that specifi c lipid species are associated with hypertension ( 15 ), central obesity ( 31 ), and type 2 diabetes ( 32 ).…”

Section: Vc Approachmentioning

confidence: 99%

Plasma lipidome is independently associated with variability in metabolic syndrome in Mexican American families

Kulkarni

Meikle

Mamtani

et al. 2014

Journal of Lipid Research

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The full spectrum of lipid molecules in human plasma and their potential role in human health and disease are areas of intense interest ( 1-9 ). This interest owes substantially to the sophisticated technologies that make it possible to accurately capture and quantify the human lipidome ( 8, 10 ). Associative evidence gleaned from plasma lipidomic studies promises vital contributions to biomarker researchan important mainstay of the continued efforts for chronic disease prevention. The plasma lipidomic profi le of humans exhibits a wide range of diversity ( 11,12 ) and is associated with several conditions including obesity ( 13, 14 ), hypertension ( 14-16 ), disorders of glucose metabolism ( 13, 17 ), metabolic syndrome (MS) ( 10, 18 ), cardiovascular diseases ( 19 ), cystic fi brosis ( 20 ), nicotine consumption ( 21 ), and response to antilipid treatment ( 22 ).Lipidomic association studies conducted in the context of families have an important consideration that the concentrations of the plasma lipid species might be phenotypically as well as genetically correlated with each other ( 23 ) especially in related individuals. In that case, it is Abstract Plasma lipidome is now increasingly recognized as a potentially important marker of chronic diseases, but the exact extent of its contribution to the interindividual phenotypic variability in family studies is unknown. Here, we used the rich data from the ongoing San Antonio Family Heart Study (SAFHS) and developed a novel statistical approach to quantify the independent and additive value of the plasma lipidome in explaining metabolic syndrome (MS) variability in Mexican American families recruited in the SAFHS. Our analytical approach included two preprocessing steps: principal components analysis of the highresolution plasma lipidomics data and construction of a subject-subject lipidomic similarity matrix. We then used the Sequential Oligogenic Linkage Analysis Routines software to model the complex family relationships, lipidomic similarities, and other important covariates in a variance components framework. Our results suggested that even after accounting for the shared genetic infl uences, indicators of lipemic status (total serum cholesterol, TGs, and HDL cholesterol), and obesity, the plasma lipidome independently explained 22% of variability in the homeostatic model of assessment-insulin resistance trait and 16% to 22% variability in glucose, insulin, and waist circumference. Our results demonstrate that plasma lipidomic studies can additively contribute to an understanding of the interindividual variability in

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“…Family members including all first-, second-, and third-degree relatives of probands 16 years of age or older and his or her spouse were invited to participate. 22 In this study, we analyzed data collected from 486 individuals participating in the third phase of the SAFHS. These individuals were taken from the 26 largest pedigrees for whom phenotypic and genotypic information was available.…”

Section: The San Antonio Family Heart Studymentioning

confidence: 99%

“…24 Individuals who reported a history of diabetes and stated that they were receiving insulin or oral antidiabetic agents were also considered to have diabetes. For additional information regarding these variables, refer to MacCluer et al 22 and Mitchell et al 23 In the third phase of the study, a total of 486 individuals from 26 families were phenotyped for serum levels of creatinine. A single-void morning urine sample was collected from each participant, and urinary albumin and creatinine levels were measured.…”

Section: The San Antonio Family Heart Studymentioning

confidence: 99%

Genome-wide scans for microalbuminuria in Mexican Americans: The San Antonio Family Heart Study

Arar

Nath

Thameem

et al. 2007

Genetics in Medicine

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Purpose: Microalbuminuria, defined as urine albumin-to-creatinine ratio of 0.03 to 0.299 mg/mg, is a major risk factor for cardiovascular disease. Several genetic epidemiological studies have established that microalbuminuria clusters in families, suggesting a genetic predisposition. Method: We estimated heritability of microalbuminuria and performed a genome-wide linkage analysis to identify chromosomal regions influencing urine albumin-tocreatinine ratio in 486 Mexican Americans from 26 multiplex families. Results: Significant heritability was demonstrated for urine albumin-to-creatinine ratio (h 2 ϭ 24%, P Ͻ 0.003) after accounting for age, sex, body mass index, triglycerides, and hypertension. Genome scan revealed significant evidence of linkage of urine albumin-tocreatinine ratio to a region on chromosome 20q12 (LOD score of 3.5, P Ͻ 0.001) near marker D20S481. This region also exhibited a LOD score of 2.8 with diabetes status as a covariate and 3.0 with hypertension status as a covariate suggesting that the effect of this locus on urine albumin-to-creatinine ratio is largely independent of diabetes and hypertension. Key Words: Microalbuminuria, albumin to creatinine ratio, cardiovascular diseases, Mexican Americans, family genetic studyMicroalbuminuria is the excretion of low but abnormal levels (Ն30 mg/day) of albumin in the urine. Microalbuminuria is defined as albumin-to-creatinine ratio of 0.03 to 0.299 mg/mg on a random sample of urine. 1 Microalbuminuria is an important independent risk factor for the development of cardiovascular disease (CVD). 2 Several studies have shown that microalbuminuria, in addition to being an independent CVD risk factor, is a significant predictor of CVD, and all-cause mortality in the diabetic and nondiabetic general population. [3][4][5] This predictive effect of microalbuminuria is independent of other known CVD risk factors such as being overweight, hypertension, hypercholesterolemia, and smoking. 6 Results from the Third Copenhagen City Heart Study indicate that even very low levels of microalbuminuria are associated with increased independent risk of CVD. 5 The European Prospective Investigation into Cancer in Norfolk study examined the relationship between microalbuminuria and the incidence of CVD in individuals aged 40 to 79 years without prevalent baseline CVD. Among the participants with baseline CVD, the independent risk of all-cause mortality associated with microalbuminuria increased by 60%, when compared with normoalbuminuric participants, 7 confirming that microalbuminuria is of prognostic value in patients with established CVD. 8 Similarly, results from the San Antonio Heart Study showed that normotensive subjects with microalbuminuria had significantly higher triglyceride concentrations and insulin levels than normotensive Mexican American and non-Hispanic white subjects without microalbuminuria, suggesting that an increased atherogenic risk factor pattern exists even in normotensive subjects with microalbuminuria. 9 In addition, population-based observat...

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Genetics of Atherosclerosis Risk Factors in Mexican Americans

Cited by 74 publications

References 20 publications

Identification of ACOX2 as a shared genetic risk factor for preeclampsia and cardiovascular disease

Identification of ACOX2 as a shared genetic risk factor for preeclampsia and cardiovascular disease

Plasma lipidome is independently associated with variability in metabolic syndrome in Mexican American families

Genome-wide scans for microalbuminuria in Mexican Americans: The San Antonio Family Heart Study

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