Association of single nucleotide polymorphisms in Neuropeptide Y (NPY) and Phosphoglycerate Mutase 2 (PGAM2) genes with growth traits in rabbits.

Genetic improvement of local rabbit breeds using modern approaches such as marker-assisted selection requires accurate and precise information about marker‒trait associations in animals with different genetic backgrounds. Therefore, this study was designed to estimate the association between two mutations located in the Neuropeptide Y (NPY, g.1778G > C) and Phosphoglycerate Mutase 2 (PGAM2, c.195 C > T) genes in New Zealand White (NZW), Baladi (BR), and V-line rabbits. The first mutation was genotyped using high-resolution melting, and the second mutation was genotyped using the PCR-RFLP method. The results revealed significant associations between the NPY mutation and body weight at 10 (V-line) and 12 weeks of age (NZW, BR, and V-line), body weight gain (BWG) from 10 to 12 weeks of age (BR), BWG from 6 to 12 weeks of age (NZW, BR, and V-line), average daily gain (NZW, BR, and V-line, and BR), growth rate (GR) from 8 to10 weeks (V-line), 10 to 12 weeks (BR), and GR from 6 to 12 weeks of age (BR, and V-line). The PGAM2 mutation was associated with body weight at 10 (V-line) and 12 (NZW, and V-line) weeks of age, with significant positive additive effects at 12 weeks of age in all breeds, and was associated with BWG from 8 to 10 and 10 to 12 in BR, and BWG from 6 to 12 weeks of age (NZW, and BR), and average daily gain (NZW, and BR), and was associated with GR form 8 to 10 weeks (BR), from10 to 12 weeks (BR, and V-line) and from 6 to 12 weeks (BR). The results highlighted the importance of the two mutations in growth development, and the possibility of considering them as candidate genes for late growth in rabbits.

Cloning of goat PGAM2 gene and its overexpression promotes the differentiation of intramuscular preadipocytes.

As a member of the PGAMs family, PGAM2 has been proved to catalyze the reversible reaction of 3-phosphoglycerate (3-PGA) to 2-phosphoglycerate (2-PGA) in the glycolytic pathway. However, it is unclear whether PGAM2 has a role in regulating differentiation in goat intramuscular preadipocytes. Here, this study was carried to clone the open reading frame (ORF) of goat PGAM2, elucidate its molecular and expressional characteristics, and evaluate the involvement in adipogenesis of intramuscular preadipocytes. According to our findings, the cloned goat PGAM2 gene was 784 bp in full length, including 762 bp of ORF and encoding a protein of 253 amino acids. The expressional level of PGAM2 peaked at 48 hours after induced adipogenic differentiation and was highest in the skeletal muscle of triceps. Moreover, overexpression of PGAM2 transfected by its overexpression plasmid promotes lipid accumulation of goat intramuscular adipocyte as shown by Oil Red O and bodipy staining, accompanied by up-regulating the mRNA levels of peroxisome proliferator-activated receptor γ (PPARγ) (p < 0.001), sterol regulatory element-binding protein 1 (SREBP1) (p < 0.001), CCAAT/Enhancer-binding protein α (C/EBPα) (p < 0.01) and lipoprotein lipase (LPL) (p < 0.01). Taken together, these findings indicate that PGAM2 is a positive regulator for goat intramuscular adipocytes and provide new insights into improvement intramuscular fat deposition in goat meat.

Phosphoglycerate mutase 2 is elevated in serum of patients with heart failure and correlates with the disease severity and patient's prognosis.

BACKGROUND: Heart failure (HF) is a serious and advanced stage of various cardiac diseases with high mortality and rehospitalization rates. Phosphoglycerate mutase 2 (PGAM2) overexpression was identified in the serum of patients with HF. MATERIAL/METHODS: One hundred and fifty-three cases of HF were included in the present work. According to New York Heart Association (NYHA) classification, 22 were grade II, 84 were grade III, and 47 were grade IV. Serum PGAM2, NT-proBNP, B-type natriuretic peptide (BNP), troponin T (TNT), and Cys-C of HF patients were detected using ELISA assay. Left ventricular ejection fraction, left ventricular end-diastolic inner diameter, and left atrium (LA) inner diameter of the included cases were also detected by the cardiac color Doppler. RESULTS: The number of patients with atrial fibrillation was significantly higher in NYHA IV group than in groups II and III with statistical difference (p < 0.05). The serum PGAM2, NT-proBNP, and Cys-C were significantly higher in NYHA IV group than in NYHA II and NYHA III groups (p all < 0.05). NT-proBNP had the highest prediction efficacy of HF severity and PGAM2 was also a potential biomarker for HF severity evaluation with relatively high sensitivity, specificity, and area under the ROC. The overall survival among NYHA II, III, and IV groups were statistically different (p = 0.04) with the median survival time of 25 months for NYHA III and IV groups. CONCLUSION: PGAM2 is a new promising biomarker for evaluation of the severity of HF. Combination detection using multiple serum factors such as PGAM2, NT-proBNP, BNP, TNT, and Cys-C can improve the HF severity differential diagnosis performance.

Targeted exome sequencing identified a novel frameshift variant in the PGAM2 gene causing glycogen storage disease type X.

BACKGROUND: Phosphoglycerate mutase (PGAM) deficiency is associated with a rare glycogen storage disease (glycogenosis type X) in humans caused by pathogenic variants in the PGAM2 gene. Several genes causing autosomal forms of glycogen storage disease (GSD) have been identified, involved in various forms of neuromuscular anomalies. METHODS: Targeted whole exome sequencing (WES) was performed on the DNA of single affected individual (IV-1) followed by Sanger sequencing confirmation of the identified variant in all available members of the family. RESULTS: In the present study, the affected individual, presenting mild features of glycogen storage disease type X. Targeted exome sequencing revealed a biallelic frameshift variant (c.687dupC; p. Met230Hisfs*6) in the PGAM2 gene located on chromosome 7p13. CONCLUSION: In short, we reported a novel homozygous frameshift variant as a cause of glycogen storage disease type X from Pakistani population. The work presented here proves significance of targeted WES in accurate diagnosis of known complex genetic disorders.

The c.-360 T>C mutation affects PGAM2 transcription activity and is linked with the water holding capacity of the longissimus lumborum muscle in pigs.

The phosphoglycerate mutase 2 (PGAM2) gene encodes a key enzyme in the glycolytic process. This study examined a functional mutation in the PGAM2 gene and evaluated its relationship with water holding capacity (WHC). RT-qPCR analysis showed the PGAM2 mRNA level was significantly higher in the low-WHC group than in the high-WHC group (P<0.05). The c.-360 T>C mutation was identified through sequencing and found to have opposite allele distributions in the two groups. The allele was further genotyped in 170 Duroc×Large White×Yorkshire crossbred pigs using allele-specific PCR. The CC genotype was associated with lower WHC and higher PGAM2 mRNA levels, whereas the TT genotype corresponded to a higher WHC and lower PGAM2 mRNA levels (P<0.05). A luciferase activity assay also showed that the CC-genotype promoter had higher activity than the TT-genotype promoter (P<0.05). In conclusion, we discovered the c.-360 T>C mutation in the PGAM2 gene, which is a promising marker for improving pork WHC.

Insulin/IGF1-PI3K-dependent nucleolar localization of a glycolytic enzyme--phosphoglycerate mutase 2, is necessary for proper structure of nucleolus and RNA synthesis.

Phosphoglycerate mutase (PGAM), a conserved, glycolytic enzyme has been found in nucleoli of cancer cells. Here, we present evidence that accumulation of PGAM in the nucleolus is a universal phenomenon concerning not only neoplastically transformed but also non-malignant cells. Nucleolar localization of the enzyme is dependent on the presence of the PGAM2 (muscle) subunit and is regulated by insulin/IGF-1-PI3K signaling pathway as well as drugs influencing ribosomal biogenesis. We document that PGAM interacts with several 40S and 60S ribosomal proteins and that silencing of PGAM2 expression results in disturbance of nucleolar structure, inhibition of RNA synthesis and decrease of the mitotic index of squamous cell carcinoma cells. We conclude that presence of PGAM in the nucleolus is a prerequisite for synthesis and initial assembly of new pre-ribosome subunits.