ABSTRACT
Blood lipids are important risk factors for coronary artery disease (CAD). Here we perform an exome-wide association study by genotyping 12,685 Chinese, using a custom Illumina HumanExome BeadChip, to identify additional loci influencing lipid levels. Single-variant association analysis on 65,671 single nucleotide polymorphisms reveals 19 loci associated with lipids at exome-wide significance (P<2.69 × 10(-7)), including three Asian-specific coding variants in known genes (CETP p.Asp459Gly, PCSK9 p.Arg93Cys and LDLR p.Arg257Trp). Furthermore, missense variants at two novel loci-PNPLA3 p.Ile148Met and PKD1L3 p.Thr429Ser-also influence levels of triglycerides and low-density lipoprotein cholesterol, respectively. Another novel gene, TEAD2, is found to be associated with high-density lipoprotein cholesterol through gene-based association analysis. Most of these newly identified coding variants show suggestive association (P<0.05) with CAD. These findings demonstrate that exome-wide genotyping on samples of non-European ancestry can identify additional population-specific possible causal variants, shedding light on novel lipid biology and CAD.
Subject(s)
Asian People/genetics , Exome/genetics , Genetic Variation , Lipid Metabolism/genetics , Cholesterol, HDL/metabolism , Cholesterol, LDL/metabolism , Genotype , Humans , Triglycerides/metabolismABSTRACT
INTRODUCTION: TRPC1 and TRPC3 proteins are widely expressed in skeletal muscles in forming calcium-permeable channels. Herein we characterize the expression pattern of TRPC transcripts during skeletal myogenesis in C2C12 myoblasts. METHODS: We used polymerase chain reaction and Western blotting to detect expression levels, immunohistochemistry for subcellular localization, and co-immunoprecipitation techniques to assess interaction. RESULTS: TRPC1 localizes to the cytoplasm and is enriched in the perinuclear region in undifferentiated myoblasts. Expression of TRPC1 increases significantly during myogenesis and resides mainly in differentiated myocytes and myotubes. TRPC3 is absent in undifferentiated myoblasts, is dramatically upregulated in differentiated culture, and is preferentially expressed in myotubes. Physical interaction of TRPC1-TRPC3 was observed, suggesting the possible existence of heteromers. CONCLUSIONS: Expression of TRPC1 and TRPC3 is tightly regulated during myogensis. Evidence of TRPC1-TRPC3 interaction was first demonstrated in a muscle cell line. The functional consequences of this interaction remain to be established.
