A gene risk score using missense variants in SLCO1B1 is associated with earlier onset statin intolerance.

Background And Aims: The efficacy of statin therapy is hindered by intolerance to the therapy, leading to discontinuation. Variants in SLCO1B1, which encodes the hepatic transporter OATB1B1, influence statin pharmacokinetics, resulting in altered plasma concentrations of the drug and its metabolites. Current pharmacogenetic guidelines require sequencing of the SLCO1B1 gene, which is more expensive and less accessible than genotyping.

Hepatocyte mARC1 promotes fatty liver disease.

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) has a prevalence of ∼25% worldwide, with significant public health consequences yet few effective treatments. Human genetics can help elucidate novel biology and identify targets for new therapeutics. Genetic variants in mitochondrial amidoxime-reducing component 1 () have been associated with NAFLD and liver-related mortality; however, its pathophysiological role and the cell type(s) mediating these effects remain unclear.

MLX plays a key role in lipid and glucose metabolism in humans: Evidence from in vitro and in vivo studies.

Background And Aim: Enhanced hepatic de novo lipogenesis (DNL) has been proposed as an underlying mechanism for the development of NAFLD and insulin resistance. Max-like protein factor X (MLX) acts as a heterodimer binding partner for glucose sensing transcription factors and inhibition of MLX or downstream targets has been shown to alleviate intrahepatic triglyceride (IHTG) accumulation in mice. However, its effect on insulin sensitivity remains unclear.

The cholesterol-lowering effect of statins is modified by intolerance genotype: Results from a recruit-by-genotype clinical trial.

Statin intolerance leads to poor adherence to statin therapy, resulting in a failure to achieve desired cholesterol reduction and adverse outcomes. The Asp247Gly genotype has been identified as being associated with statin intolerance and statin-induced myalgia. We conducted a randomized clinical trial to examine its role in immune response through T regulatory cell aggregation and in achieving cholesterol reduction targets.

Common Statin Intolerance Variants in and Show Synergistic Effects on Statin Response: An Observational Study Using Electronic Health Records.

Statin intolerance impacts approximately 10% of statin users, with side effects ranging from mild myalgia to extreme intolerance resulting in myopathy and rhabdomyolysis. Statin intolerance results in poor adherence to therapy and can impact statin efficacy. Many genetic variants are associated with statin intolerance.

LTA4H rs2660845 association with montelukast response in early and late-onset asthma.

Leukotrienes play a central pathophysiological role in both paediatric and adult asthma. However, 35% to 78% of asthmatics do not respond to leukotriene inhibitors. In this study we tested the role of the LTA4H regulatory variant rs2660845 and age of asthma onset in response to montelukast in ethnically diverse populations.

Polymorphism in Locus Modifies Risk of Atrial Fibrillation in Patients on Thyroid Hormone Replacement Therapy.

Aims: Atrial fibrillation (AF) is a risk for patients receiving thyroid hormone replacement therapy. No published work has focused on pharmacogenetics relevant to thyroid dysfunction and AF risk. We aimed to assess the effect of L-thyroxine on AF risk stratified by a variation in a candidate gene.

Pharmacogenomics of statin-related myopathy: Meta-analysis of rare variants from whole-exome sequencing.

Aims: Statin-related myopathy (SRM), which includes rhabdomyolysis, is an uncommon but important adverse drug reaction because the number of people prescribed statins world-wide is large. Previous association studies of common genetic variants have had limited success in identifying a genetic basis for this adverse drug reaction. We conducted a multi-site whole-exome sequencing study to investigate whether rare coding variants confer an increased risk of SRM.

Genome-wide association mapping for type and mammary health traits in French dairy goats identifies a pleiotropic region on chromosome 19 in the Saanen breed.

Type traits and mammary health traits are important to dairy ruminant breeding because they influence animal health, milking ability, and longevity, as well as the economic sustainability of farms. The availability of the genomic sequence and a single nucleotide polymorphism chip in goats has opened up new fields of investigation to better understand the genes and mechanisms that underlie such complex traits and to be able to select them. Our objective was to perform a genome-wide association study in dairy goats for 11 type traits and somatic cell count (SCC) as proxies for mastitis resistance.

Author Correction: A genome scan for milk production traits in dairy goats reveals two new mutations in Dgat1 reducing milk fat content.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

A common missense variant of LILRB5 is associated with statin intolerance and myalgia.

Aims: A genetic variant in LILRB5 (leukocyte immunoglobulin-like receptor subfamily-B) (rs12975366: T > C: Asp247Gly) has been reported to be associated with lower creatine phosphokinase (CK) and lactate dehydrogenase (LDH) levels. Both biomarkers are released from injured muscle tissue, making this variant a potential candidate for susceptibility to muscle-related symptoms. We examined the association of this variant with statin intolerance ascertained from electronic medical records in the GoDARTS study.

Glu83Gly Is Associated With Blunted Creatine Kinase Variation, but Not With Myalgia.

Background: To test the association of a recently reported variant in the creatine kinase (CK) muscle gene, Glu83Gly (rs11559024) with constitutive creatine phosphokinase (CK) levels, CK variation, and inducibility. Given the diagnostic importance of CK in determining muscle damage, we tested the association of the variant with myalgia.

Methods And Results: Meta-analysis between longitudinal cohort GoDARTS (Genetics of Diabetes Audit and Research, Tayside Scotland), minor allele frequency (=0.

A genome scan for milk production traits in dairy goats reveals two new mutations in Dgat1 reducing milk fat content.

The quantity of milk and milk fat and proteins are particularly important traits in dairy livestock. However, little is known about the regions of the genome that influence these traits in goats. We conducted a genome wide association study in French goats and identified 109 regions associated with dairy traits.