Genetic regulation of adipose tissue transcript expression is involved in modulating serum triglyceride and HDL-cholesterol

Sajuthi, Satria; Sharma, Neeraj Kumar; Comeau, Mary E.; Chou, Jeff W.; Bowden, Donald W.; Freedman, Barry I.; Langefeld, Carl D.; Parks, John S.; Das, Swapan K.

doi:10.1016/j.gene.2017.08.019

Cited by 10 publications

(9 citation statements)

References 36 publications

(50 reference statements)

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“…Additionally, in immunoinflammatory pathways, genes were activated among individuals with higher serum TG levels. 29 Furthermore, in this study, the genotypes GA and AA of rs2710642 and genotypes TC and CC of rs10496099 were correlated with low serum TG levels in the Maonan population and some haplotypes of EHBP1 rs2710642 and rs10496099 SNPs modulated serum lipid levels. As a dominant haplotype in both the Han and Maonan populations, rs2710642A− rs10496099C was a potential protective factor for slightly increasing serum ApoA1 or HDL-C levels and decreasing TC and TG levels, but rs2710642G−rs10496099C was a damaging factor with the opposite trendsdecreasing HDL-C and increasing TC, TG, or LDL-C serum levels.…”

Section: ■ Discussionsupporting

confidence: 48%

“…Blood lipids also circulate to damaged intima and are retained in the intima, mainly triggering atherosclerosis, CVD, and ischemic stroke. Additionally, in immunoinflammatory pathways, genes were activated among individuals with higher serum TG levels . Furthermore, in this study, the genotypes GA and AA of rs2710642 and genotypes TC and CC of rs10496099 were correlated with low serum TG levels in the Maonan population and some haplotypes of EHBP1 rs2710642 and rs10496099 SNPs modulated serum lipid levels.…”

Section: Discussionmentioning

confidence: 49%

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EHBP1 SNPs, Their Haplotypes, and Gene–Environment Interactive Effects on Serum Lipid Levels

et al. 2020

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The associations between single nucleotide polymorphisms (SNPs) rs2710642 and rs10496099 and their effect on the EH domain-binding protein 1 (EHBP1) gene and serum lipid profiles remain uncertain. This study was performed to investigate the two EHBP1 SNPs in Han and Maonan populations, including their association, haplotypes, and effects on serum lipid levels. Two EHBP1 SNPs in 564 Han and 796 Maonan participants were genotyped by high-throughput sequencing, and then the genotype and haplotype distributions of two EHBP1 SNPs were analyzed. Moreover, risk factors and their effects on serum lipid levels were analyzed using multivariable linear regression and logistic regression analyses. In Han and Maonan populations, a significant difference was found in the allelic and genotypic frequencies of the EHBP1 rs2710642 and rs10496099 SNPs and the alternate alleles of rs2710642A and rs10496099C might be potentially beneficial for healthy lipid levels. Medium linkage disequilibrium between the two SNPs was noted in each ethnic group, and four main haplotypes were detected. The rs2710642G–rs10496099C haplotype was associated with high triglycerides (TGs) and low high-density lipoprotein cholesterol, and the rs2710642A–rs10496099C haplotype was associated with low TGs and high apolipoprotein A1. The rs2710642G–rs10496099C haplotype was a high-risk factor for hyperlipidemia, and it interacted with smoking, fasting blood glucose, and hypertension to increase but with the female factor to decrease the prevalence of hyperlipidemia in Han individuals. The EHBP1 rs2710642 and rs10496099 SNPs and gene–environment interactions were associated with serum lipid profiles and hyperlipidemia, which is of ethnic specificity to our study populations.

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Section: ■ Discussionsupporting

confidence: 48%

Section: Discussionmentioning

confidence: 49%

EHBP1 SNPs, Their Haplotypes, and Gene–Environment Interactive Effects on Serum Lipid Levels

et al. 2020

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“…Published evidence implicated these 18 genes directly through population studies (GBP6, GSTO1, HHIPL1, INTS10, RGS16 and RNU6-679P), indirectly through association with other metabolic conditions (CCDC69, DNAH2, GALNT17, HERC5, KIF5C, MARCH2 and PRDM14) or through association with complications of T2D (CASC15, CCDC107, MIR147A, PFKFB3 and RNF166). Detailed annotation of the published literature in this regard is provided in Supplementary Table S3 ) [ 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 ]. From the remaining genes identified to be significantly associated with T2D in this study, there were two open reading frames, three long intergenic non-coding elements and a pseudogene.…”

Section: Resultsmentioning

confidence: 99%

Susceptibility Loci for Type 2 Diabetes in the Ethnically Endogamous Indian Sindhi Population: A Pooled Blood Genome-Wide Association Study

Pipal

Mamtani

Patel

et al. 2022

Genes

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Type 2 diabetes (T2D) is a complex metabolic derangement that has a strong genetic basis. There is substantial population-specificity in the association of genetic variants with T2D. The Indian urban Sindhi population is at a high risk of T2D. The genetic basis of T2D in this population is unknown. We interrogated 28 pooled whole blood genomes of 1402 participants from the Diabetes In Sindhi Families In Nagpur (DISFIN) study using Illumina’s Global Screening Array. From a total of 608,550 biallelic variants, 140 were significantly associated with T2D after adjusting for comorbidities, batch effects, pooling error, kinship status and pooling variation in a random effects multivariable logistic regression framework. Of the 102 well-characterized genes that these variants mapped onto, 70 genes have been previously reported to be associated with T2D to varying degrees with known functional relevance. Excluding open reading frames, intergenic non-coding elements and pseudogenes, our study identified 22 novel candidate genes in the Sindhi population studied. Our study thus points to the potential, interesting candidate genes associated with T2D in an ethnically endogamous population. These candidate genes need to be fully investigated in future studies.

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“…Therefore, the present study focused on identifying transcriptional mechanisms associated with composite gluco-metabolic phenotypes. Our previous studies showed that a subset of gluco-metabolic trait GWAS-identified SNPs are cis-eSNPs ( 11 ; 31 ). Herein, we demonstrate that expression of a subset of CP-associated transcripts is determined by cis-eSNPs, and CP-associated transcripts are among the genes predicted by bioinformatics analysis of GWAS-implicated BMI loci.…”

Section: Discussionmentioning

confidence: 99%

Transcriptional Regulatory Mechanisms in Adipose and Muscle Tissue Associated with Composite Glucometabolic Phenotypes

Langefeld

Comeau

Sharma

et al. 2018

Obesity

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ObjectiveTissue-specific gene expression is associated with individual metabolic measures. However, these measures may not reflect the true but latent underlying biological phenotype. This study reports gene expression associations with multi-dimensional gluco-metabolic characterizations of obesity, glucose homeostasis, and lipid traits.MethodsFactor analysis was computed using orthogonal rotation to construct composite phenotypes (CPs) from 23 traits in 256 non-diabetic African Americans. Genome-wide transcript expression data from adipose and muscle were tested for association with CPs, and expression quantitative trait loci (eQTL) were identified by association between cis-SNPs and gene expression.ResultsThe factor analysis identified six CPs. The CPs 1 through 6 individually explained 34%, 12%, 9%, 8%, 6% and 5% of the variation in 23 gluco-metabolic traits studied. There were 3994 and 929 CP–associated transcripts identified in adipose and muscle, respectively; CP2 had the largest number of associated transcripts. Pathway analysis identified multiple canonical pathways from the CP-associated transcripts. In adipose and muscle, significant cis-eQTL were identified for 558 and 164 CP-associated transcripts (q-value <0.01), respectively.ConclusionsAdipose and muscle transcripts comprehensively define pathways involved in regulating gluco-metabolic disorders. Cis-eQTLs for CP-associated eGenes may act as primary causal determinants of gluco-metabolic phenotypes by regulating transcription of key genes.

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Genetic regulation of adipose tissue transcript expression is involved in modulating serum triglyceride and HDL-cholesterol

Cited by 10 publications

References 36 publications

EHBP1 SNPs, Their Haplotypes, and Gene–Environment Interactive Effects on Serum Lipid Levels

EHBP1 SNPs, Their Haplotypes, and Gene–Environment Interactive Effects on Serum Lipid Levels

Susceptibility Loci for Type 2 Diabetes in the Ethnically Endogamous Indian Sindhi Population: A Pooled Blood Genome-Wide Association Study

Transcriptional Regulatory Mechanisms in Adipose and Muscle Tissue Associated with Composite Glucometabolic Phenotypes

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