Quantitative trait loci influencing low density lipoprotein particle size in African Americans

Kullo, Iftikhar J.; Ding, Keyue; Boerwinkle, Eric; Turner, Stephen T.; Andrade, Mariza de

doi:10.1194/jlr.m600078-jlr200

Cited by 10 publications

(9 citation statements)

References 41 publications

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“…Interestingly, the 9p LOD-1 intervals for the modest LDL mean particle size and TG concentration signals overlap with a linkage signal for TG in African-Americans ( 58 ) and encompass a region previously associated with CAD and T2DM ( 59 ). There do not appear to be any other overlaps with prior linkage studies in African-derived populations of standard lipid panel traits (60)(61)(62)(63)(64) or lipoprotein subclasses determined using polyacrylamide gel electrophoresis ( 29 ). However, evidence of linkage in this region was previously found in four large multi-generational pedigrees of European descent ( 65 ).…”

Section: Bivariate Linkage Analysismentioning

confidence: 55%

“…First, in insulin-resistant individuals, the NMR lipoprotein subclass profi le indicated that large VLDL particles, produced primarily by the liver, are markedly increased without consistent changes in medium or small VLDL. This is important because large VLDL particles may confer more cardiovascular disease risk ( 29,30 ). Second, the NMR data demonstrated a shift of LDL particles from large, buoyant particles to small, dense particles, with the net result of little or no change in overall LDL-cholesterol.…”

Section: Subjectsmentioning

confidence: 95%

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The genetic architecture of lipoprotein subclasses in Gullah-speaking African American families enriched for type 2 diabetes: The Sea Islands Genetic African American Registry (Project SuGAR)

Divers

Sale

et al. 2010

Journal of Lipid Research

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This article is available online at http://www.jlr.org studied in this sample and that novel loci on chromosomes 6, 10, 16, and 20 may harbor genes contributing to small, atherogenic LDL particle concentration and large, triglyceride-rich VLDL particle concentration. Cardiovascular disease (CVD) is the leading cause of morbidity and mortality among individuals with diabetes ( 1-3 ). For example, the risk of coronary heart disease is 2-4 times higher in diabetic patients compared with nondiabetic individuals ( 4-8 ). Dyslipidemia is thought to be a potential common link between these two conditions ( 9, 10 ). The principal lipoprotein classes, VLDL, LDL, and HDL, have received considerable attention as cardiovascular disease risk factors in the epidemiology literature. Several genes have also been reported to be associated with these lipoprotein phenotypes ( 11-13 ). In fact, genetic correlation and genes with possible pleiotropic effect on LDL, Abstract We sought to partition the genetic and environmental infl uences on lipoprotein subclasses and identify genomic regions that may harbor genetic variants that infl uence serum lipoprotein levels in a sample of Gullah-speaking African-Americans. We genotyped 5,974 SNPs in 979 subjects from 418 pedigrees and used the variance component approach to compute heritability estimates, genetic and environmental correlations, and linkage analyses for selected lipoprotein subclasses. The highest heritability estimate was observed for large VLDL particle concentration (0.56 ± 0.14). Mean LDL particle size and small LDL particle concentration ( ؊ 0.94) had the strongest genetic correlation estimate. The highest logarithm of odds (LOD) score detected (3.0) was on chromosome 6p24 for small LDL particle concentration. The strongest signal, obtained with the reduced sample of diabetic individuals only, was observed on chromosome 20p13 for small LDL particle concentration. The highest bivariate linkage signal (LOD 2.4) was observed on chromosome 6p24 for mean LDL particle size and small LDL particle concentration.jlr Our results suggest a significant genetic contribution to multiple lipoprotein subclasses

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Section: Bivariate Linkage Analysismentioning

confidence: 55%

Section: Subjectsmentioning

confidence: 95%

The genetic architecture of lipoprotein subclasses in Gullah-speaking African American families enriched for type 2 diabetes: The Sea Islands Genetic African American Registry (Project SuGAR)

Divers

Sale

et al. 2010

Journal of Lipid Research

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“…IPA is a knowledge-based discovery tool and the largest curated database of previously published findings on mammalian biology. [30][31][32] The CRP gene was located under the linkage signal for CRP on chromosome 1q21-23, but we did not find a linkage signal for the region on chromsome 4q28 that harbors the genes encoding fibrinogene peptides (FGA, FGB, and FGG). Seven genes (FCER1G, SELP, SERPINC1, ITGB3, GH1, SCARB1, and TCF1) involved in the expression, activation, and degradation of fibrinogen were identified under the linkage signals for plasma fibrinogen (Table 4).…”

Section: Potential Candidate Genes In the Linked Regionsmentioning

confidence: 60%

Genomic regions that influence plasma levels of inflammatory markers in hypertensive sibships

et al. 2007

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We performed univariate and bivariate linkage analyses to identify genomic regions that may influence plasma levels of C-reactive protein (CRP) and fibrinogen and exert pleiotropic effects on the two traits. Subjects included African Americans (AA, n=1310, mean age 62.7±9.4 years) and non-Hispanic whites (NHW, n = 796 mean age 58.4±9.8 years) belonging to hypertensive sibships. Plasma CRP was measured by an immunoturbidimetric assay and fibrinogen by the Clauss method. Genotyping was performed at 366 microsatellite marker loci spaced ~10 cM apart across the 22 autosomes. Estimation of heritability and linkage analyses were performed using a variance components approach. Moderate heritability was noted for CRP (0.38 in AA, 0.37 in NHW) and fibrinogen (0.44 in AA, 0.28 in NHW). Significant genetic correlation between CRP and fibrinogen was present in both AA (0.39) and NHW (0.40). In univariate linkage analysis, the maximum logarithm of odds (LOD) score for CRP was on chromosome 10q22 in NHW (LOD = 1.69, 106.75 cM, P = 0.0026) and for fibrinogen on chromosome 2 in AA (LOD = 2.14, 55.5 cM, P = 0.0009). Bivariate linkage analysis demonstrated suggestive evidence of linkage (defined as LOD score ≥2.87) for both traits on chromosome 12 (LOD = 3.44, 152.16 cM, P = 0.0003) in AA and on chromosome 21 (LOD = 3.03, 13.05 cM, P = 0.0008) in NHW. Plasma CRP and fibrinogen levels are heritable and genetically correlated. Linkage analyses identified several chromosomal regions that may harbor genes influencing CRP and fibrinogen levels and exert pleiotropic effects on the two traits.

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“…Other genome-wide linkage screens in different populations reported evidence of linkage for plasma triglyceride levels on chromosomes 2p, 2q, 3q, 6q, 8q, 9q, 10p, 10q, 11p, 11q, 17q, and 19q (5)(6)(7)(8)(9)(10)(11). With the exception of 2q, 6q, and 10q, the majority of these loci appear to have no strong effects in the Mexican Americans.…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, a study in a Chinese population from the Hong Kong Family Diabetes Study identified several chromosomes, including 2q, 3q, 6q, 9q, 10q, and 17q, containing genes that influence variation in triglyceride levels (7). Other evidence for the linkage of plasma triglyceride levels has been reported on 8q in African Americans (8), 2q in Hutterites (9), 11q in Old Order Amish (10), and 10p in Finnish families (11). More recently, a meta-analysis of genome-wide linkage studies for plasma triglyceride levels provided suggestive evidence for linkage at chromosome 7p (12).…”

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confidence: 99%

Genome-Wide Linkage Scan for Genes Influencing Plasma Triglyceride Levels in the Veterans Administration Genetic Epidemiology Study

Coletta

Schneider

et al. 2009

Diabetes

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OBJECTIVE— Elevated plasma triglyceride concentration is a component of the insulin resistance syndrome and is commonly associated with type 2 diabetes, obesity, and coronary heart disease. The goal of our study was to perform a genome-wide linkage scan to identify genetic regions that influence variation in plasma triglyceride levels in families that are enriched with individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS— We used phenotypic and genotypic data from 1,026 individuals distributed across 294 Mexican-American families, who were ascertained for type 2 diabetes, from the Veterans Administration Genetic Epidemiology Study (VAGES). Plasma triglyceride values were transformed, and a variance-components technique was used to conduct multipoint linkage analysis. RESULTS— After adjusting for the significant effects of sex and BMI, heritability for plasma triglycerides was estimated as 46 ± 7% ( P < 0.0001). Multipoint linkage analysis yielded the strongest evidence for linkage of plasma triglycerides near marker D12S391 on chromosome 12p (logarithm of odds [LOD] = 2.4). Our linkage signal on chromosome 12p provides independent replication of a similar finding in another Mexican-American sample from the San Antonio Family Diabetes Study (SAFDS). Combined multipoint linkage analysis of the VAGES and SAFDS data yielded significant evidence for linkage of plasma triglycerides to a genetic location between markers GATA49D12 and D12S391 on 12p (LOD = 3.8, empirical P value = 2.0 × 10 −5 ). This region on 12p harbors the gene-encoding adiponectin receptor 2 ( AdipoR2 ), where we previously have shown that multiple single nucleotide polymorphisms are associated with plasma triglyceride concentrations in the SAFDS. In the present study, we provided suggestive evidence in favor of association for rs929434 with triglyceride concentrations in the VAGES. CONCLUSIONS— Collectively, these results provide strong evidence for a major locus on chromosome 12p that influences plasma triglyceride levels in Mexican Americans.

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Quantitative trait loci influencing low density lipoprotein particle size in African Americans

Cited by 10 publications

References 41 publications

The genetic architecture of lipoprotein subclasses in Gullah-speaking African American families enriched for type 2 diabetes: The Sea Islands Genetic African American Registry (Project SuGAR)

The genetic architecture of lipoprotein subclasses in Gullah-speaking African American families enriched for type 2 diabetes: The Sea Islands Genetic African American Registry (Project SuGAR)

Genomic regions that influence plasma levels of inflammatory markers in hypertensive sibships

Genome-Wide Linkage Scan for Genes Influencing Plasma Triglyceride Levels in the Veterans Administration Genetic Epidemiology Study

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