Редактирование: MYBPC3

Myosin-binding protein C, cardiac-type (Cardiac MyBP-C) (C-protein, cardiac muscle isoform)

==Publications==

{{medline-entry
|title=Compound heterozygosity deteriorates phenotypes of hypertrophic cardiomyopathy with founder [[MYBPC3]] mutation: evidence from patients and zebrafish models.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/25281569
|abstract=Although most founder mutation carriers of hypertrophic cardiomyopathy (HCM), such as the cardiac myosin-binding protein C gene ([[MYBPC3]]), arose from a common ancestor exhibit favorable clinical phenotypes, there still remain small fractions of these carriers associated with increased cardiovascular events. However, few data exist regarding the defining factors that modify phenotypes of these patients, particularly in terms of multiple gene mutations. Therefore, we assessed genotype-phenotype correlations and investigated factors that contribute to phenotypic diversities of mutation carriers from 488 unrelated HCM probands. A prevalent founder mutation (Val762Asp) in [[MYBPC3]] was identified in 33 subjects from 19 families. Among them, 28 carriers harbored an isolated Val762Asp mutation and exhibited a late onset of overt HCM compared with other [[MYBPC3]] mutation carriers (62.8 ± 3.0 vs 50.1 ± 2.6 yr, P < 0.05). In contrast, the remaining five carriers had additional sarcomere gene mutations (3 carriers in [[MYBPC3]] and 2 carriers in the cardiac troponin T gene). Of these five carriers, two carriers showed early disease onset and one carrier exhibited end-stage HCM. These phenotypes were recapitulated in zebrafish models; injection of [[MYBPC3]] Val762Asp alone did not alter ventricular size or function, but ventricular dimension was significantly increased when [[MYBPC3]] Val762Asp mRNA was coinjected with [[MYBPC3]] Arg820Gln mRNA. These results demonstrate that [[MYBPC3]] Val762Asp may be associated with unfavorable HCM phenotypes in some cases when combined with another [[MYBPC3]] mutation. 
|mesh-terms=* Adult
* Aged
* Aging
* Animals
* Cardiomyopathy, Hypertrophic, Familial
* Carrier Proteins
* Female
* Genotype
* Heterozygote
* Humans
* Male
* Middle Aged
* Mutation
* Pedigree
* Phenotype
* Sarcomeres
* Zebrafish
|keywords=* cardiac remodeling
* compound heterozygotes
* hypertrophic cardiomyopathy
* myosin-binding protein C
|full-text-url=https://sci-hub.do/10.1152/ajpheart.00637.2013
}}
{{medline-entry
|title=Association of levels of fasting glucose and insulin with rare variants at the chromosome 11p11.2-[[MADD]] locus: Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium Targeted Sequencing Study.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/24951664
|abstract=Common variation at the 11p11.2 locus, encompassing [[MADD]], [[ACP2]], [[NR1H3]], [[MYBPC3]], and [[SPI1]], has been associated in genome-wide association studies with fasting glucose and insulin (FI). In the Cohorts for Heart and Aging Research in Genomic Epidemiology Targeted Sequencing Study, we sequenced 5 gene regions at 11p11.2 to identify rare, potentially functional variants influencing fasting glucose or FI levels. Sequencing (mean depth, 38×) across 16.1 kb in 3566 individuals without diabetes mellitus identified 653 variants, 79.9% of which were rare (minor allele frequency <1%) and novel. We analyzed rare variants in 5 gene regions with FI or fasting glucose using the sequence kernel association test. At [[NR1H3]], 53 rare variants were jointly associated with FI (P=2.73×10(-3)); of these, 7 were predicted to have regulatory function and showed association with FI (P=1.28×10(-3)). Conditioning on 2 previously associated variants at [[MADD]] (rs7944584, rs10838687) did not attenuate this association, suggesting that there are >2 independent signals at 11p11.2. One predicted regulatory variant, chr11:47227430 (hg18; minor allele frequency=0.00068), contributed 20.6% to the overall sequence kernel association test score at [[NR1H3]], lies in intron 2 of [[NR1H3]], and is a predicted binding site for forkhead box A1 ([[FOXA1]]), a transcription factor associated with insulin regulation. In human HepG2 hepatoma cells, the rare chr11:47227430 A allele disrupted [[FOXA1]] binding and reduced [[FOXA1]]-dependent transcriptional activity. Sequencing at 11p11.2-[[NR1H3]] identified rare variation associated with FI. One variant, chr11:47227430, seems to be functional, with the rare A allele reducing transcription factor [[FOXA1]] binding and [[FOXA1]]-dependent transcriptional activity.
|mesh-terms=* Aged
* Aged, 80 and over
* Aging
* Blood Glucose
* Chromosomes, Human, Pair 11
* Cohort Studies
* Death Domain Receptor Signaling Adaptor Proteins
* Diabetes Mellitus, Type 2
* Fasting
* Female
* Gene Frequency
* Genetic Variation
* Genome-Wide Association Study
* Genomics
* Guanine Nucleotide Exchange Factors
* Heart Diseases
* Humans
* Insulin
* Male
* Middle Aged
* Polymorphism, Single Nucleotide
* Sequence Analysis, DNA
|keywords=* genetic epidemiology
* glucose
* human genetics
* insulin
* molecular genetics
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4066205
}}