ArticleBMC medical genomics2013
A comprehensive analysis of adiponectin QTLs using SNP association, SNP cis-effects on peripheral blood gene expression and gene expression correlation identified novel metabolic syndrome (MetS) genes with potential role in carcinogenesis and systemic inflammation.
Article in BMC medical genomics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 2 of them syntheses that pooled it.
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12 citing papers in PubMed, 2 syntheses or guidelines pooled it, 57 citations in OpenAlex.
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- Heterogeneity in susceptibility to polycystic ovary syndrome among women with epilepsy.Acta epileptologica · 2023Article
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- Distinct Associations of BMI and Fatty Acids With DNA Methylation in Fasting and Postprandial States in Men.Frontiers in genetics · 2021Article
- Aldo-Keto Reductase 1C1 (International journal of molecular sciences · 2020Article
- The metabolic network coherence of human transcriptomes is associated with genetic variation at the cadherin 18 locus.Human genetics · 2019Article
- Review
- Humanity in a Dish: Population Genetics with iPSCs.Trends in cell biology · 2018Review
- Expression of candidate genes associated with obesity in peripheral white blood cells of Mexican children.Archives of medical science : AMS · 2016Article
- F-box/LRR-repeat protein 7 is genetically associated with Alzheimer's disease.Annals of clinical and translational neurology · 2015Article
- Article
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundMetabolic syndrome (MetS) is an aberration associated with increased risk for cancer and inflammation. Adiponectin, an adipocyte-produced abundant protein hormone, has countering effect on the diabetogenic and atherogenic components of MetS. Plasma levels of adiponectin are negatively correlated with onset of cancer and cancer patient mortality. We previously performed microsatellite linkage analyses using adiponectin as a surrogate marker and revealed two QTLs on chr5 (5p14) and chr14 (14q13).
methodsUsing individuals from 85 extended families that contributed to the linkage and who were measured for 42 clinical and biologic MetS phenotypes, we tested QTL-based SNP associations, peripheral white blood cell (PWBC) gene expression, and the effects of cis-acting SNPs on gene expression to discover genomic elements that could affect the pathophysiology and complications of MetS.
resultsAdiponectin levels were found to be highly intercorrelated phenotypically with the majority of MetS traits. QTL-specific haplotype-tagging SNPs associated with MetS phenotypes were annotated to 14 genes whose function could influence MetS biology as well as oncogenesis or inflammation. These were mechanistically categorized into four groups: cell-cell adhesion and mobility, signal transduction, transcription and protein sorting. Four genes were highly prioritized: cadherin 18 (CDH18), myosin X (MYO10), anchor protein 6 of AMPK (AKAP6), and neuronal PAS domain protein 3 (NPAS3). PWBC expression was detectable only for the following genes with multi-organ or with multi-function properties: NPAS3, MARCH6, MYO10 and FBXL7. Strong evidence of cis-effects on the expression of MYO10 in PWBC was found with SNPs clustered near the gene's transcription start site. MYO10 expression in PWBC was marginally correlated with body composition (p = 0.065) and adipokine levels in the periphery (p = 0.064). Variants of genes AKAP6, NPAS3, MARCH6 and FBXL7 have been previously reported to be associated with insulin resistance, inflammatory markers or adiposity studies using genome-wide approaches whereas associations of CDH18 and MYO10 with MetS traits have not been reported before.
conclusionsAdiponectin QTLs-based SNP association and mRNA expression identified genes that could mediate the association between MetS and cancer or inflammation.
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