👤 Andrea L Jorgensen

APOE genotype may affect statin therapy response. We conducted a meta-analysis to update and quantify this association across various outcomes. We searched seven databases (MEDLINE, Scopus, Web of Science, the Cochrane Library, APA PsycINFO, CINAHL Plus and ClinicalTrials.gov) on 9 May 2024. Screening and data extraction were performed by two reviewers and a machine learning tool (ASReview). From 4352 de-duplicated records, 52 studies were included in the meta-analysis. Biomarkers analysed included low-density lipoprotein cholesterol (LDLC), total cholesterol (TC), triglycerides (TG) and high-density lipoprotein cholesterol (HDLC). Compared to ε3 carriers, ε2 carriers showed greater reductions in LDLC in response to statin treatment (mean difference in percentage change: -2.98%, 95% CI: -5.88% to -0.08%) and similar reductions in TC (-2.73%, -5.62% to 0.16%), and TG (-4.95%, -11.93% to 2.04%) with no significant difference in HDLC (-0.09%, -3.10% to 2.91%). After adjusting for publication bias, ε4 carriers showed less pronounced statin effects, with smaller reductions in LDLC (mean difference: 10.04%, 6.04% to 14.04%), TC (8.99%, 5.08% to 12.90%) and TG (8.24%, 2.15% to 14.33%), along with a smaller increase in HDLC (-10.08%, -15.30% to -4.85%) compared to ε3 carriers. Study quality was unclear, and heterogeneity (partly explained by sex and Familial hypercholesterolemia) was high, especially for the percentage changes. A stronger genotype effect was seen in males. Our meta-analysis shows that APOE genotype may influence statin response, emphasizing the need to incorporate known genetic factors into personalized treatment regimens. Show less

In rodent models of type 2 diabetes (T2D), sustained remission of hyperglycemia can be induced by a single intracerebroventricular (icv) injection of fibroblast growth factor 1 (FGF1), and the mediobasal hypothalamus (MBH) was recently implicated as the brain area responsible for this effect. To better understand the cellular response to FGF1 in the MBH, we sequenced >79,000 single-cell transcriptomes from the hypothalamus of diabetic Lep Show less

Peanut allergy (PA) is a complex disease with both environmental and genetic risk factors. Previously, PA loci were identified in filaggrin (FLG) and HLA in candidate gene studies, and loci in HLA were identified in a genome-wide association study and meta-analysis. We sought to investigate genetic susceptibility to PA. Eight hundred fifty cases and 926 hyper-control subjects and more than 7.8 million genotyped and imputed single nucleotide polymorphisms (SNPs) were analyzed in a genome-wide association study to identify susceptibility variants for PA in the Canadian population. A meta-analysis of 2 phenotypes (PA and food allergy) was conducted by using 7 studies from the Canadian, American (n = 2), Australian, German, and Dutch (n = 2) populations. An SNP near integrin α6 (ITGA6) reached genome-wide significance with PA (P = 1.80 × 10 This study identifies multiple novel loci as risk factors for PA and food allergy and establishes C11orf30 as a risk locus for both PA and food allergy. Multiple genes (C11orf30/EMSY, SKAP1, and CTNNA3) identified by this study are involved in epigenetic regulation of gene expression. Show less