Genetic loci for blood lipid levels identified by linkage and association analyses in Caribbean Hispanics

Dong, Chuanhui; Beecham, Ashley; Wang, Liyong; Slifer, Susan H.; Wright, Clinton B.; Blanton, Susan H.; Rundek, Tatjana; Sacco, Ralph L.

doi:10.1194/jlr.p013672

Cited by 26 publications

(19 citation statements)

References 62 publications

(43 reference statements)

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“…The relationship between CDH13 variants and cholesterol level has not been well established. However, Dong, et al21 recently demonstrated that two SNPs of CDH13 , rs4357934 and rs1164264, were significantly associated with total and LDL-C levels. This may be possible evidence that supports our data.…”

Section: Discussionmentioning

confidence: 99%

Association betweenCDH13Variants and Cardiometabolic and Vascular Phenotypes in a Korean Population

et al. 2013

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PurposeAlthough some CDH13 single nucleotide polymorphisms (SNPs) have been shown to be determinants of blood adiponectin levels, the clinical implications of CDH13 variants are not yet completely understood. The purpose of this study was to evaluate the effects of SNPs of CDH13 on metabolic and vascular phenotypes.Materials and MethodsWe included 238 hypertensive subjects and 260 age- and sex-matched controls. Seven tagging-SNPs were identified in the CDH13 gene by whole gene sequencing. The association between these SNP variants and the risk of hypertension, metabolic traits, and carotid intima-media thickness (IMT) was examined.ResultsMinor allele carriers of rs12444338 had a lower risk of hypertension, but the association turned out just marginal after adjusting confoudners. Blood glucose levels were higher in the minor allele carriers of c.1407C>T (p=0.01), whereas low-density lipoprotein-cholesterol levels were greater in those of rs6565105 (p=0.02). The minor allele of rs1048612 was associated with a higher body mass index (p=0.01). In addition, the mean carotid IMT was significantly associated with rs12444338 (p=0.02) and rs1048612 (p=0.02).ConclusionThese results provide evidence that CDH13 variants are associated with metabolic traits and carotid atherosclerosis in Koreans. This study shows the multifaceted effects of CDH13 variants on cardiometabolic risk.

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Section: Discussionmentioning

confidence: 99%

Association betweenCDH13Variants and Cardiometabolic and Vascular Phenotypes in a Korean Population

et al. 2013

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“…Subjects included in this study were drawn from the population-based North Manhattan Study (NOMAS) [16, 17]. In brief, NOMAS participants had never been diagnosed with a stroke, were at least 40 years of age, and resided for at least 3 months in a household with a telephone in Northern Manhattan.…”

Section: Methodsmentioning

confidence: 99%

Genetic variants in LEKR1 and GALNT10 modulate sex-difference in carotid intima-media thickness: A genome-wide interaction study

et al. 2015

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Background There is an established sex-difference in carotid artery intima-media thickness (cIMT), a recognized marker of subclinical atherosclerosis. However, the genetic underpinnings of sex-differences in gene-IMT associations are largely unknown. Methods With a multistage design using 731,037 single nucleotide polymorphisms (SNP), a genome wide interaction study was performed in a discovery sample of 931 unrelated Hispanics, followed by replication in 153 non-Hispanic whites and 257 non-Hispanic blacks. Assuming an additive genetic model, we tested for sex–SNP interactions on cIMT using regression analysis. Results We did not identify any genome-wide significant SNPs but identified 14 loci with suggestive significance. Specifically, SNP-by-sex interaction was found for rs7616559 within LEKR1 gene (P=3.5E-06 in Hispanic discovery sample, P=0.018 in White, and P=1.3E-06 in combined analysis) and for rs2081015 located within GALNT10 gene (P=4.5E-06 in Hispanic discovery sample, P=0.042 in Blacks, and P=5.3E-07 in combined analysis). For rs7616559 within LEKR1, men had greater cIMT than women in G allele carriers (beta±SE: 0.044±0.007, P=4.2E-09 in AG carriers; beta±SE: 0.064±0.007, P=6.2E-05 in GG carriers). For rs2081015 within GALNT10, men had greater cIMT than women in C allele carriers (beta±SE: 0.022±0.007, P=0.002 in CT carriers; beta±SE: 0.051±0.008, P=3.1E-10 in CC carriers). Conclusions Our genome-wide interaction analysis reveals multiple loci that may modulate sex difference in cIMT. Of them, genetic variants on LEKR1 and GALNT10 genes have been associated with control of adiposity and weight. Given the consistent findings across different-ethnic groups, further studies are warranted to perform investigations of functional genetic variants in these regions.

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“…We found suggestive evidence of linkage of LOD score>2.0 on 15q23 for TG, 16q23 for LDL-C, 19q12 for TC and LDL-C, and 20p12 for LDL-C. In the association analysis of the linkage peaks, we also found that seven SNPs near FLJ45974 were associated with LDL-C/HDL-C with a nominal P<3.5×10 −5 , in addition to associations (P<0.0001) for other lipid traits with SNPs in or near CDH13 , SUMF2 , TLE3 , FAH , ARNT2 , TSHZ3 , ZNF343 , RPL7AL2 , and TMC3 genes [64]. Replication of these genes is still required in other populations before specifically targeting them for intervention.…”

Section: Introductionmentioning

confidence: 76%

“…Moreover, studies demonstrated that lipid traits have a significant genetic component, with the estimates of heritability of 40–70% for total cholesterol (TC), 30–70% for LDL-C, 30–60% for high-density lipoprotein cholesterol (HDL-C), 20–55% for triglycerides (TG), and 30–50% for LDL-C/HDL-C [60-62]. In NOMAS, first we have demonstrated the strong association between lipids and apolipoproteins with CP as phenotype of atherosclerosis [63], and then we identified genetic loci affecting blood lipid levels among Caribbean Hispanics [64]. We found suggestive evidence of linkage of LOD score>2.0 on 15q23 for TG, 16q23 for LDL-C, 19q12 for TC and LDL-C, and 20p12 for LDL-C.…”

Section: Introductionmentioning

confidence: 99%

Genetic susceptibility to cerebrovascular disease

Della-Morte

Pacifici

Rundek

2016

Current Opinion in Lipidology

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Purpose of review Cerebrovascular Disease (CeVD) remains a major cause of death and a leading cause of disability worldwide. CeVD is a complex and multifactorial disease caused by the interaction of vascular risk factors, environment and genetic factors. In the present article we discussed genetic susceptibility to CeVD, with particular emphasis on genetic studies of the associations between lipid traits and CeVD. Recent findings Several animal and clinical studies clearly defined genetic predisposition to atherosclerosis and CeVD, and particularly to ischemic stroke. Recent evidence has shown that traditional vascular risk factors explain only a small proportion of variance in atherosclerosis, suggesting that additional non-traditional factors and novel genetic determinants impact CeVD. With the help of genome-wide technology, novel genetic variants have been implicated in CeVD and lipid metabolism such as those in protein convertase subtilisin/kexin type 9 (PCSK9) gene in stroke and familial hypercholesterolemia. These studies are important since they contribute to our understanding of the genetic mechanisms underlying CeVD and to developing more effective CeVD prevention strategies. Summary CeVD is a complex and multifactorial disease and genetics likely plays an important role in its pathogenesis. The gene–gene and gene–environment interactions of genes involved in biology of vascular disease including the lipid metabolism are important factors for individual susceptibility to CeVD. Accounting for individual variation in genes, environment and lifestyle will bring us closer to precision medicine, which is an emerging and recently introduced new approach for disease treatment and prevention in clinical practice.

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Genetic loci for blood lipid levels identified by linkage and association analyses in Caribbean Hispanics

Cited by 26 publications

References 62 publications

Association betweenCDH13Variants and Cardiometabolic and Vascular Phenotypes in a Korean Population

Association betweenCDH13Variants and Cardiometabolic and Vascular Phenotypes in a Korean Population

Genetic variants in LEKR1 and GALNT10 modulate sex-difference in carotid intima-media thickness: A genome-wide interaction study

Genetic susceptibility to cerebrovascular disease

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