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

Zhang, Yi; Kent, Jack W.; Olivier, Michael; Ali, Omar; Cerjak, Diana; Broeckel, Ulrich; Abdou, Reham; Dyer, Thomas D.; Comuzzie, Anthony G.; Curran, Joanne E.; Carless, Melanie A.; Rainwater, David L.; Göring, Harald H.H.; Blangero, John; Kissebah, Ahmed H.

doi:10.1186/1755-8794-6-14

Cited by 24 publications

(20 citation statements)

References 68 publications

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“…On the other hand, the mRNA abundance of Cdh18 and Cyp2b13 was increased. In line with this result, the abundance of Cdh18 transcript has been associated with features of metabolic syndrome, with a potential role in systemic inflammation . The overexpression of Cyp2b13 is also consistent with its ranking among the top 15 upregulated genes in the liver of diabetic mice .…”

Section: Resultssupporting

confidence: 73%

A readout of metabolic efficiency in arylamine N‐acetyltransferase‐deficient mice reveals minor energy metabolism changes

et al. 2019

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Recent studies have revealed a possible link between the activities of polymorphic arylamine N‐acetyltransferases (NATs) and energy metabolism. We used a Nat1/Nat2 double knockout (KO) mouse model to demonstrate that ablation of the two Nat genes is associated with modest, intermittent alterations in respiratory exchange rate. Pyruvate tolerance tests show that double KO mice have attenuated hepatic gluconeogenesis when maintained on a high‐fat/high‐sucrose diet. Absence of the two Nat genes also leads to an increase in the hepatic concentration of coenzyme A in mice fed a high‐fat/high‐sucrose diet. Our results suggest a modest involvement of NAT in energy metabolism in mice, which is consistent with the absence of major phenotypic deregulation of energy metabolism in slow human acetylators.

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Section: Resultssupporting

confidence: 73%

A readout of metabolic efficiency in arylamine N‐acetyltransferase‐deficient mice reveals minor energy metabolism changes

et al. 2019

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“…33 SNPs within CDH18 have previously been associated with increased BMI 34,35 and waist circumference. 35 SOX11 is a transcription factor involved in embryonic 36 and adult neurogenesis 37 and is expressed in proliferating progenitor and immature neurons during migration and during dendritic and axonal growth, and it is up-regulated after peripheral nerve injury. 38 Because both CDH18 and SOX11 appear to influence neuronal growth, repair, and connectivity, these genes may be important regulators of neuronal response to radiation-induced damage among CCS.…”

Section: Discussionmentioning

confidence: 99%

“…CDH18 is a classical cadherin expressed in the brain and has been implicated in synapse formation and neuroplasticity . SNPs within CDH18 have previously been associated with increased BMI and waist circumference . SOX11 is a transcription factor involved in embryonic and adult neurogenesis and is expressed in proliferating progenitor and immature neurons during migration and during dendritic and axonal growth, and it is up‐regulated after peripheral nerve injury .…”

Section: Discussionmentioning

confidence: 99%

Genetic and clinical factors associated with obesity among adult survivors of childhood cancer: A report from the St. Jude Lifetime Cohort

Wilson

Liu

Yang

et al. 2015

Cancer

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Purpose We aimed to identify treatment and genetic factors associated with obesity among childhood cancer survivors. Methods Participants included 1996 survivors previously treated for cancer at St. Jude Children’s Research Hospital who survived ≥10 years from diagnosis (median age at diagnosis 7.2 years, median age at follow-up 32.4 years). Obesity was defined as a body mass index ≥30kg/m2. Factors associated with adult obesity were identified by subgroup-specific (cranial radiation (CRT) exposure status) multivariable logistic regression. Single nucleotide polymorphisms (SNPs) associated with obesity were identified by subgroup-specific exploratory genome-wide association analyses (two-stage resampling approach with type I error rate=5×10−6). Results Forty-seven percent and 29.4% of survivors treated with or without receive CRT were obese at evaluation, respectively. In multivariable analyses, abdominal/pelvic radiation exposure was associated with decreased prevalence of obesity among survivors regardless of cranial radiation (p<0.0001). The odds of obesity were increased among survivors treated with CRT who had also received glucocorticoids (p=0.014), or who were younger at diagnosis (p=0.013). Among survivors treated with CRT, 166 SNPs were associated with obesity. The strongest association was observed with rs35669975 (p=3.3×10−8) on 13q33.3, approximately 30kb downstream of FAM155A. SNPs within GLRA3, and near SOX11 and CDH18 were also identified. These genes have been implicated in neural growth, repair, and connectivity. Conclusion Obesity in childhood cancer survivors remains associated with previous CRT and glucocorticoid exposures. Genetic variants related to neural connectivity may modify the risk of obesity among survivors treated with cranial radiation. Validation of our findings in independent cohorts is required.

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“…Cis ‐phase interaction may play an important role in the pathogenicity of complex trait disease. For example, Zhang et al tested the effects of cis ‐acting SNPs on several gene expressions in peripheral white blood cell, and a significant difference of cis ‐effects on the MYO10 gene expression was firstly found to be correlated with metabolic syndrome. A cis ‐phase interaction between VNTR polymorphism and functional SNPs was also identified within the MAOA gene in major depressive disorder .…”

Section: Discussionmentioning

confidence: 99%

The involvement of ADAMTS‐5 genetic polymorphisms in predisposition and diffusion tensor imaging alterations of lumbar disc degeneration

Chen

Líu

et al. 2014

Journal Orthopaedic Research

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Purpose: Low back pain is a global health problem in which more than 40% is caused by lumbar intervertebral disc degeneration (LDD). ADAMTS-5 (A disintegrin and metalloproteinase with thrombospondin motifs-5) was shown to be involved in LDD by functional analyses. To identify whether there is an association between ADAMTS-5 and LDD, and what is the contribution of ADAMTS-5 genetic polymorphisms to MD (Mean diffusivity) changes in lumbar IVD (Intervertebral disc). We firstly genotyped selected ADAMTS-5 SNPs (Single nucleotide polymorphisms) in a Chinese Han population. After the primary analyses of allelic, genotypic, and haplotypic association, we performed SNP-SNP interaction analysis. We subsequently genotyped another 50 participants and acquired the corresponding MD values from individual lumbar IVDs. The association analysis between the genotypic groups divided by the above positive SNPs and the corresponding MD values were also performed. Significant associations were identified in rs151058, rs229052, and rs162502. None of the 2-SNP haplotypic analysis survived the 10,000 permutation test. The following interaction analysis demonstrated that rs151058 was strong associated with LDD when conditioning on rs162502. Significant difference of MD values between AA and Gþ carriers was identified in rs162502. This is the first study indicating that the SNPs of ADAMTS-5 may contribute to predisposition of LDD. An interaction between rs151058 and rs229052 may exist in ADAMTS-5 with LDD. Keywords: lumbar disc degeneration (LDD); a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5); single nucleotide polymorphism (SNP); diffusion tensor imaging (DTI) As a global health problem, low back pain (LBP) was reported to affect about 80% of population during a lifetime.1 LBP, defined as pain radiating from the back into the dermatome of the affected nerve trunk, is a common musculoskeletal disorder characterized by symptomatic lumbar disc herniation with or without sciatica.2 More than 40% of LBP is caused by lumbar intervertebral disc degeneration (LDD). 3It was reported that about 5% of the Finnish population suffered from LDD, leading to disability in the workingage population. 4 Though several environmental and anthropometric risk factors have been showed to be related to LDD, the roles of genetic factors can never be exaggerated. 5-10The extracellular matrix (ECM), composed of collagens and proteoglycans, is crucial to normal intervertebral disc (IVD) functions.11 Previous studies indicated that the synthesis and degradation balance of ECM was interrupted by diverse matrix proteases during LDD. [12][13][14][15][16] As a large family of metalloproteases, ADAMTS-5 seems to be the most active one, 15,17,18 and has been paid increasing attentions due to their abilities in the cartilage proteoglycan cleavage. 19,20 Besides mRNA and protein of ADAMTS-5 were detected in IVDs, 21 increased levels in patients with chronic LBP and intervertebral disc herniation during LDD can be found. [22][23][24...

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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

Cited by 24 publications

References 68 publications

A readout of metabolic efficiency in arylamine N‐acetyltransferase‐deficient mice reveals minor energy metabolism changes

A readout of metabolic efficiency in arylamine N‐acetyltransferase‐deficient mice reveals minor energy metabolism changes

Genetic and clinical factors associated with obesity among adult survivors of childhood cancer: A report from the St. Jude Lifetime Cohort

The involvement of ADAMTS‐5 genetic polymorphisms in predisposition and diffusion tensor imaging alterations of lumbar disc degeneration

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