ABSTRACT
This study aimed to explore the relationship between genetic changes and high-altitude pulmonary edema (HAPE) susceptibility, and to screen for the key single nucleotide polymorphism (SNP) loci in the HAPE-susceptibility gene, by investigating the SNPs occurring in hypoxia-related genes in HAPE-susceptible and control (non-susceptible) populations. This research was conducted on Han recruits, who travelled to the Lhasa plateau (altitude, 3658 m). Ten loci located on ten genes extracted from the HAPE and healthy populations were amplified by polymerase chain reaction, and subsequently sequenced. The investigated genes included those coding for aldosterone synthase 2 (CYP11B2), angiotensin-converting enzyme (ACE), heat-shock protein 70 (HSP70), nuclear factor kappa B (NF-κB), surfactant protein A2 (SP-A2), plasminogen activator inhibitor-1 (PAI-1), nitric oxide synthetase (NOS), vascular endothelial growth factor (VEGF), prolyl hydroxylase (EGLN1), and zinc finger protein A20. The gene distribution of each SNP loci and its correlation with HAPE was analyzed. Statistical analyses of the genotype frequencies of the SNPs revealed significant differences in the ACE (rs4309), EGLN1 (rs480902), SP-A2 (rs1965708), HSP70 (rs1008438), PAI-1 (rs1799889), and NOS (rs199983) expressions between the HAPE and healthy control groups (P < 0.05); therefore, these SNP loci were believed to indicate HAPE susceptibility. HAPE is correlated with multiple- SNP loci. A correlation analysis between genetic polymorphism and HAPE susceptibility revealed that 6 hypoxia-related genes were key sites accounting for HAPE. These findings could help assess the risk of HAPE in populations expressing different genotypes, in order to reduce the occurrence of HAPE.
Subject(s)
Altitude , Genetic Predisposition to Disease , Hypoxia/genetics , Polymorphism, Single Nucleotide/genetics , Pulmonary Edema/genetics , Acute Disease , Alleles , Base Sequence , DNA Mutational Analysis , DNA-Binding Proteins/genetics , Gene Frequency/genetics , Genetic Loci , HSP70 Heat-Shock Proteins/genetics , Heterozygote , Homozygote , Humans , Intracellular Signaling Peptides and Proteins/genetics , Molecular Sequence Data , NF-kappa B/genetics , Nitric Oxide Synthase/genetics , Nuclear Proteins/genetics , Peptidyl-Dipeptidase A/genetics , Plasminogen Activator Inhibitor 1/genetics , Prolyl Hydroxylases/genetics , Promoter Regions, Genetic/genetics , Pulmonary Surfactant-Associated Protein A/genetics , Tumor Necrosis Factor alpha-Induced Protein 3 , Vascular Endothelial Growth Factor A/geneticsABSTRACT
We examined the expression of myosin heavy chain (MyHC) isoforms and forkhead box transcription factor O1 (FoxO1) in porcine soleus and extensor digitorum longus (EDL) muscles to clarify the correlation of FoxO1 and the relative abundance of transcripts of MyHC isoforms. Soleus muscle was found to be redder than EDL muscles in pigs, and immunohistochemical fast MyHC staining showed more oxidative type I fibers compared to EDL. qRT-PCR quantification of MyHC isoforms I, IIa, IIx, and IIb showed that expression of MyHC I and MyHC IIa mRNAs was much higher, whereas expression of MyHC IIx and MyHC IIb mRNAs was much lower in porcine soleus muscle compared to EDL muscle. Expression of FoxO1 mRNA and p-FoxO1 protein was significantly more abundant in porcine soleus muscle compared to EDL muscle. The expression of phosphorylated FoxO1 (p-FoxO1) was positively correlated with the expression of MyHC I (R = 0.9747, P < 0.01) and negatively correlated with the expression of MyHC IIx (R = -0.9963, P < 0.01) and MyHC IIb (R = -0.9834, P < 0.01). Taken together, these results suggested that FoxO1 may play a pivotal role in the determination of muscle fiber type.
Subject(s)
Forkhead Transcription Factors/genetics , Forkhead Transcription Factors/metabolism , Muscle, Skeletal/metabolism , Myosin Heavy Chains/genetics , Swine/genetics , Animals , Male , Muscle, Skeletal/cytology , Myosin Heavy Chains/metabolism , Organ Specificity , Phosphorylation , Protein Isoforms/metabolism , Swine/metabolismABSTRACT
To better understand the function of the myostatin gene and its promoter region in bovine, we amplified and sequenced the myostatin gene and promoter from the blood of Qinchuan and Red Angus cattle by using polymerase chain reaction. The sequences of Qinchuan and Red Angus cattle were compared with those of other cattle breeds available in GenBank. Exon splice sites were confirmed by mRNA sequencing. Compared to the published sequence (GenBank accession No. AF320998), 69 single nucleotide polymorphisms (SNPs) were identified in the Qinchuan myostatin gene, only one of which was an insertion mutation in Qinchuan cattle. There was a 16-bp insertion in the first 705-bp intron in 3 Qinchuan cattle. A total of 7 SNPs were identified in exon 3, in which the mutation occurred in the third base of the codon and was synonymous. On comparing the Qinchuan myostatin gene sequence to that of Red Angus cattle, a total of 50 SNPs were identified in the first and third exons. In addition, there were 18 SNPs identified in the Qinchuan cattle promoter region compared with those of other cattle compared to the Red Angus cattle myostatin promoter region. breeds (GenBank accession No. AF348479), but only 14 SNPs when compared to the Red Angus cattle myostatin promoter region.