Context: Lamins are essential for nuclear shape and function. Polymorphisms in LMNA may associate with fat and muscle development and aging.
Objective: Our aim was to determine the influence of LMNA rs4641 on lean body mass (LBM) and fat mass (FM), in vivo metabolism, and expression of LMNA transcripts in human skeletal muscle.
Design: We genotyped LMNA rs4641 in 196 Danish twins who were extensively phenotypically characterized. We measured mRNA levels of LMNA transcripts, lamin A and C, in basal and insulin-stimulated skeletal muscle biopsies.
Results: The rs4641 T-allele was associated with increased weight and body mass index (P=0.02), including increased FM (P=0.03) and LBM (P=0.004). Impact of rs4641 on FM was seen primarily among elderly twins. The T-allele was associated with elevated fasting plasma insulin levels (P=0.01) and homeostasis model of insulin resistance (P=0.02) in young twins. T-allele carriers did not exhibit consistent changes of first phase insulin secretion, nor did they exhibit significant peripheral or hepatic insulin resistance, and rs4641 did not influence muscle lamin A or C mRNA levels. The lamin A-to-C mRNA ratio was increased with acute insulin stimulation (P<0.0005), and the lamin A and C mRNA levels were diminished in young compared to elderly twins (P<0.001).
Conclusions: The LMNA rs4641 T-allele is associated with increased LBM and FM with more fat relative to muscle in elderly twins, which may impact risk of type 2 diabetes. Increased mRNA levels of lamins with age may counteract muscle wasting, and influence of insulin on lamin A-to-C ratio suggests a role in cytoskeletal muscle protein regulation.
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http://dx.doi.org/10.1210/jc.2009-2675 | DOI Listing |
Genet Mol Res
November 2015
Fu Wai Hospital Sino-German Laboratory, Beijing, China.
Recently, studies on the pathogenesis of dilated cardiomyopathy (DCM) have focused on the underlying molecular biology and the association between single nucleotide polymorphisms (SNPs) and disease. This study was designed to explore the association between the rs4641 SNP of the LMNA gene and DCM in order to identify a new gene locus related to DCM. Polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing were employed to detect and genotype rs4641 in 198 patients with DCM and 160 healthy controls.
View Article and Find Full Text PDFInt J Clin Exp Med
September 2015
Shanghai Children's Hospital, Shanghai Jiaotong University Shanghai 200040, China.
Objective: To investigate whether LMNA gene mutation is associated with dilated cardiomyopathy (DCM) in Chinese Han Race children.
Methods: DNA was isolated from 78 patients with DCM and 100 healthy Chinese children who served as controls. 12 exons in the functional regions and the adjacent part of introns of the LMNA gene were amplified with polymerase chain reactions (PCR) and the PCR products were sequenced with DNA sequencer.
Int J Cardiol Heart Vasc
June 2015
Biophysics & Structural Genomics Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata 700064, India.
Background: Dilated Cardiomyopathy (DCM) is one of the most commonly encountered heart diseases reported globally. It is characterized by enlarged ventricles with impaired systolic and diastolic functions. Mutations in gene are one of the causative factors to precipitate the disease.
View Article and Find Full Text PDFZhonghua Xin Xue Guan Bing Za Zhi
March 2014
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Objective: To explore the association between LMNA gene mutation and familiar dilated cardiomyopathy (DCM) (FDCM) and idiopathic DCM (IDCM) in Uygurs and Hans people in Xinjiang area.
Methods: Peripheral blood samples were collected from 28 family member with FDCM and 123 sporadic patients with IDCM(56 Uygur patients and 67 Han patients), 80 Uygur and 80 Han people were chosen as normal controls. PCR was used to amplify the 12 exons of LMNA gene.
PLoS One
January 2012
Department of Biosciences and Nutrition, Center for Biosciences, Karolinska Institutet, Huddinge, Sweden.
Today, there are at least a dozen different genetic disorders caused by mutations within the LMNA gene, and collectively, they are named laminopathies. Interestingly, the same mutation can cause phenotypes with different severities or even different disorders and might, in some cases, be asymptomatic. We hypothesized that one possible contributing mechanism for this phenotypic variability could be the existence of high and low expressing alleles in the LMNA locus.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!