Dataset Information

Association of common variants in the human eyes shut ortholog (EYS) with statin-induced myopathy: evidence for additional functions of EYS.

ABSTRACT: Of the nearly 38 million people in the USA who receive statin therapy, 0.1-0.5% experience severe or life-threatening myopathic side effects.We performed a genome-wide association study (GWAS) in a group of patients with severe statin myopathy versus a statin-tolerant group to identify genetic susceptibility loci.Replication studies in independent groups of severe statin myopathy (n = 190) and statin-tolerant controls (n = 130) resulted in the identification of three single-nucleotide polymorphisms (SNPs), rs9342288, rs1337512, and rs3857532, in the eyes shut homolog (EYS) on chromosome 6 suggestive of an association with risk for severe statin myopathy (P = 0.0003-0.0008). Analysis of EYS cDNA demonstrated that EYS gene products are complex and expressed with relative abundance in the spinal cord as well as in the retina.Structural similarities of these EYS gene products to members of the Notch signaling pathway and to agrin suggest a possible functional role in the maintenance and regeneration of the structural integrity of skeletal muscle.

SUBMITTER: Isackson PJ

PROVIDER: S-EPMC3175321 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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Publications

Association of common variants in the human eyes shut ortholog (EYS) with statin-induced myopathy: evidence for additional functions of EYS.

Isackson Paul J PJ Ochs-Balcom Heather M HM Ma Changxing C Harley John B JB Peltier Wendy W Tarnopolsky Mark M Sripathi Naganand N Wortmann Robert L RL Simmons Zachary Z Wilson Jon D JD Smith Stephen A SA Barboi Alexandru A Fine Edward E Baer Alan A Baker Steven S Kaufman Kenneth K Cobb Beth B Kilpatrick Jeffrey R JR Vladutiu Georgirene D GD

Muscle & nerve 20110808 4

<h4>Introduction</h4>Of the nearly 38 million people in the USA who receive statin therapy, 0.1-0.5% experience severe or life-threatening myopathic side effects.<h4>Methods</h4>We performed a genome-wide association study (GWAS) in a group of patients with severe statin myopathy versus a statin-tolerant group to identify genetic susceptibility loci.<h4>Results</h4>Replication studies in independent groups of severe statin myopathy (n = 190) and statin-tolerant controls (n = 130) resulted in the ...[more]

PMID: 21826682

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Project description:The perceived emotional value of stimuli and, as a consequence the subjective emotional experience with them, can be affected by context-dependent styles of processing. Therefore, the investigation of the neural correlates of emotional experience requires accounting for such a variable, a matter of an experimental challenge. Closing the eyes affects the style of attending to auditory stimuli by modifying the perceptual relationship with the environment without changing the stimulus itself. In the current study, we used fMRI to characterize the neural mediators of such modification on the experience of emotionality in music. We assumed that closed eyes position will reveal interplay between different levels of neural processing of emotions. More specifically, we focused on the amygdala as a central node of the limbic system and on its co-activation with the Locus Ceruleus (LC) and Ventral Prefrontal Cortex (VPFC); regions involved in processing of, respectively, 'low', visceral-, and 'high', cognitive-related, values of emotional stimuli. Fifteen healthy subjects listened to negative and neutral music excerpts with eyes closed or open. As expected, behavioral results showed that closing the eyes while listening to emotional music resulted in enhanced rating of emotionality, specifically of negative music. In correspondence, fMRI results showed greater activation in the amygdala when subjects listened to the emotional music with eyes closed relative to eyes open. More so, by using voxel-based correlation and a dynamic causal model analyses we demonstrated that increased amygdala activation to negative music with eyes closed led to increased activations in the LC and VPFC. This finding supports a system-based model of perceived emotionality in which the amygdala has a central role in mediating the effect of context-based processing style by recruiting neural operations involved in both visceral (i.e. 'low') and cognitive (i.e. 'high') related processes of emotions.

Dataset Information

Association of common variants in the human eyes shut ortholog (EYS) with statin-induced myopathy: evidence for additional functions of EYS.

Publications

Association of common variants in the human eyes shut ortholog (EYS) with statin-induced myopathy: evidence for additional functions of EYS.

Similar Datasets

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