E. A. Lee

Effects of variation in porcine MYOD1 gene on muscle fiber characteristics, lean meat production, and meat quality traits.

Three single nucleotide polymorphisms (SNPs) in the porcine MYOD1 gene were used for association analysis and haplotype construction to evaluate the effects of their substitution. Four hundred and three pigs of Yorkshire and Berkshire breeds were used. The mRNA expression levels of MYOD1 were examined. The g.489C>T and g.1264C>A SNPs were significantly associated with several muscle fiber characteristics, the loin eye area, and lightness. Particularly, animals having hetero-genotypes of both sites showed good performance both in lean meat production and meat quality traits. The results of haplotype substitution were similar to the associations of individual SNPs. Moreover, the 2 SNPs had significant effects on mRNA expression. Therefore, the g.489C>T and g.1264C>A SNPs in MYOD1 may be meaningful DNA markers that can be used for improving important porcine economic traits.

The Association of Klotho Polymorphism with Disease Progression and Mortality in IgA Nephropathy

Backgrounds: IgA nephropathy (IgAN) is the most common primary glomerulonephritis causing end stage renal disease (ESRD), and vasculopathy is known to involve disease progression. Klotho, a gene related to aging, has been reported to play a role in atherosclerosis and endothelial dysfunction. We investigated whether klotho gene polymorphism affect clinical course of IgAN. Methods: The data registered for PREMIER study which enrolled the patients with biopsy proven IgAN were analyzed. Two single nucleotide polymorphisms for klotho gene, G395A of promoter region and C1818T of exon 4, were examined, and investigated the association klotho genotypes with the progression of IgAN and patient survival. Results: Clinical data from 973 patients confirmed about survival were analyzed. The allele frequency was 0.830 and 0.170 for allele G and A, and 0.816 and 0.184 for allele C and T, which were complied with Hardy-Weinberg equilibrium (p=0.996 and 0.531 respectively). Death was observed more frequently in A-allele carriers of G395A polymorphism (0.7 vs 2.6 %, GG vs GA+AA, p=0.022). Renal survival in Kaplan-Meier survival curve was also worse in same group (p=0.04). Conclusion: Klotho gene polymorphism was associated with patient survival and disease progression of IgAN.

The association of Klotho gene polymorphism with the mortality of patients on maintenance dialysis

Despite medical progress, high morbidity and mortality rates have persisted in patients with end-stage renal disease (ESRD). The role in atherosclerosis and cardiovascular disease of klotho, an aging process-related gene, has been highlighted. Genetic variation in klotho has been reported to be a risk factor for coronary artery disease and ischemic stroke. Regarding the significance of cardiovascular disease for the outcome of ESRD patients, we investigated whether genetic variation of klotho was associated with mortality in ESRD patients on hemodialysis. 478 patients on maintenance hemodialysis for more than 3 months at dialysis facilities affiliated with the Western Dialysis Physician Association were enrolled in September 2004. Patient survival was checked annually until September 2007. Genotypings of klotho in terms of G395A in the promoter region, C1818T in exon 4, and KL-VS was performed. 45 deaths (11.2%) occurred over 3 years. Mortality was higher in the GA+AA group than in the GG group (18.9% vs. 6.7%, respectively, p < 0.001). Kaplan-Meier analysis also revealed that the survival of the GA+AA group was worse than that of GG group (p = 0.002). Coxs proportional hazards regression analysis showed that age, A allele carrier status in G395A of klotho, hemoglobin, albumin and HDL cholesterol levels were the significant factors affecting survival of hemodialysis patients. The A allele of the G395A polymorphism of klotho may be associated with the risk of mortality in Korean hemodialysis patients. Age, hemoglobin, albumin and HDLC were also significant prognostic factors for survival in the present study.

A Candidate Single Nucleotide Polymorphism in the 3′ Untranslated Region of Stearoyl-CoA Desaturase Gene for Fatness Quality and the Gene Expression in Berkshire Pigs

Fatness qualities in pigs measured by the amount of fat deposition and composition of fatty acids (FAs) in pork have considerable effect on current breeding goals. The stearoyl-CoA desaturase (SCD) gene plays a crucial role in the conversion of saturated FAs into monounsaturated FAs (MUFAs), and hence, is among the candidate genes responsible for pig fatness traits. Here, we identified a single nucleotide polymorphism (SNP, c.*2041T>C) in the 3′ untranslated region by direct sequencing focused on coding and regulatory regions of porcine SCD. According to the association analysis using a hundred of Berkshire pigs, the SNP was significantly associated with FA composition (MUFAs and polyunsaturated FAs [PUFAs]), polyunsaturated to saturated (P:S) FA ratio, n-6:n-3 FA ratio, and extent of fat deposition such as intramuscular fat and marbling (p<0.05). In addition, the SNP showed a significant effect on the SCD mRNA expression levels (p = 0.041). Based on our results, we suggest that the SCD c.*2041T>C SNP plays a role in the gene regulation and affects the fatness qualities in Berkshire pigs.

Predicting postoperative total calcium requirements after parathyroidectomy in secondary hyperparathyroidism.

Background/Aims: To prevent hypocalcemia after parathyroidectomy (PTX), parenteral calcium is required in addition to oral calcitriol and calcium. After switching to oral calcium, patients can be discharged from the hospital. The aim of this study was to analyze the clinical characteristics and outcomes of PTX performed at a single Korean center and to investigate the associated laboratory factors used to analyze the total amount of postoperative calcium required. Methods: We enrolled 91 hemodialysis patients undergoing PTX from November 2003 to December 2011. We collected clinical and laboratory data preoperatively, 12 and 48 hours postoperatively, at discharge, and 3 and 6 months postoperatively. Results: In total, 59 patients underwent PTX with autotransplantation (AT), 6 underwent total PTX without AT, 11 underwent subtotal PTX, and 15 underwent limited PTX. Total PTX without AT showed the lowest recurrence rate. At all postoperative time points, the mean levels of serum calcium, phosphorus, and intact parathyroid hormone (iPTH) decreased significantly, compared with preoperative levels; however, alkaline phosphatase (ALP) increased significantly from 48 hours postoperatively to discharge (p < 0.001). On multiple linear regression analysis, the total amount of injected calcium during hospitalization showed a significant correlation with preoperative ALP (p < 0.001), preoperative iPTH (p = 0.037), and Δphosphorus at 48 hours (p < 0.001). We developed an equation for estimating the total calcium requirement after PTX. Conclusions: Preoperative ALP, preoperative iPTH, and Δphosphorus at 48 hours may be significant factors in estimating the postoperative calcium requirement. The formula for postoperative calcium requirement after PTX may help to predict the duration of postoperative hospitalization.

Effects of intergenic single nucleotide polymorphisms in the fast myosin heavy chain cluster on muscle fiber characteristics and meat quality in Berkshire pigs

The heterogeneity of myosin heavy chain (MyHC) isoforms is closely related to muscle fiber characteristics, and meat quality in pigs. The fast MyHC gene cluster on porcine chromosome 12 contains MYH2, MYH1, and MYH4, which encode three fast MyHC isoforms expressed in adult skeletal muscle. Here, we identified four intergenic single nucleotide polymorphisms (SNPs) in the gene cluster. Of these, SNP1 and SNP2, which were located near MYH2, were genotyped in 199 Berkshire pigs. SNP1 were significantly associated with the total fiber number (P=0.046) and intramuscular fat contents (P=0.041), and SNP2 had significant effects on type I fiber number/area compositions (P=0.039 and P=0.041, respectively), water holding capacity (drip loss, P=0.045; cooking loss, P=0.001), and meat color (P=0.003). Taken together, our results suggest that the intergenic SNPs near MYH2 can affect muscle fiber formation and meat quality by modifying the regulatory elements of this gene cluster in pigs.

Correlations among various blood parameters at exsanguination and their relationships to pork quality traits

The objectives of this study were to investigate the correlations between various blood parameters compared with cortisol and lactate levels under the standard pre-slaughter procedure and handling conditions and to assess their potential as indicators of pork quality traits. Despite there being no additional pre-slaughter stress treatment, there is considerable variation in blood parameters at exsanguination. Serum cortisol and blood lactate levels, widely used indicators of stress, were positively correlated with blood glucose and electrolytes, such as calcium, potassium and sodium. Moreover, these parameters were significantly correlated with a rapid rate of early postmortem glycolysis and reduced water-holding capacity. In particular, blood lactate and glucose levels significantly differed between porcine quality classes. However, other blood parameters including electrolytes did not significantly differ between quality classes though they significantly correlated with pork quality traits. Therefore, serum cortisol, blood lactate and glucose have potential as indicators of the rate and extent of postmortem metabolism and ultimate pork quality under the standard procedure and handling conditions of pre-slaughter.

Diameter of parathyroid glands measured by computed tomography as a predictive indicator for response to cinacalcet in dialysis patients with secondary hyperparathyroidism.

Background/Aims: Cinacalcet is one of the important treatments of secondary hyperparathyroidism (SHPT). We evaluated the role of computed tomography (CT) for parathyroid glands (PTGs) to determine the response to cinacalcet therapy in dialysis patients. Methods: In study 1, we compared the predictive cutoff values of the largest volume or diameter of PTGs on ultrasonography or CT for achievement of target intact parathyroid hormone (iPTH) level according to K/DOQI guideline after cinacalcet treatment in a single dialysis center. In study 2, the role of the cutoff diameter of PTGs on CT in predicting responsive to cinacalcet therapy was reevaluated in dialysis patients with SHPT in multiple centers. Results: In study 1, among the total population of 26 patients, the number of patients with baseline iPTH over 600 pg/mL was 16 (61%). In study 2, it was 45 (54%), among 82 patients. In study 1, the number of PTGs equal to or larger than the cutoff value (≥ 11.2 mm) on CT, not ultrasonography, was significantly higher in non-responders than in responders (p=0.038). In study 2, the proportion of patients with PTGs ≥ 11.2 mm on CT was significantly higher in non-responders than responders (p=0.003). Multivariate analysis showed that pretreatment iPTH (odds ratio [OR] 1.498, p=0.003) and the existence of enlarged PTGs on CT (OR 8.940, p=0.015) were significant clinical factors affecting the response to cinacalcet. Conclusions: The diameter of PTGs on CT could predict the response to cinacalcet in dialysis patients with SHPT.

Estimation of Pork Quality Traits Using Exsanguination Blood and Postmortem Muscle Metabolites

The current study was designed to estimate the pork quality traits using metabolites from exsanguination blood and postmortem muscle simultaneously under the Korean standard pre- and post-slaughter conditions. A total of 111 Yorkshire (pure breed and castrated male) pigs were evaluated under the Korean standard conditions. Measurements were taken of the levels of blood glucose and lactate at exsanguination, and muscle glycogen and lactate content at 45 min and 24 h postmortem. Certain pork quality traits were also evaluated. Correlation analysis and multiple regression analysis including stepwise regression were performed. Exsanguination blood glucose and lactate levels were positively correlated with each other, negatively related to postmortem muscle glycogen content and positively associated with postmortem muscle lactate content. A rapid and extended postmortem glycolysis was associated with high levels of blood glucose and lactate, with high muscle lactate content, and with low muscle glycogen content during postmortem. In addition, these were also correlated with paler meat color and reduced water holding capacity. The results of multiple regression analyses also showed that metabolites in exsanguination blood and postmortem muscle explained variations in pork quality traits. Especially, levels of blood glucose and lactate and content of muscle glycogen at early postmortem were significantly associated with an elevated early glycolytic rate. Furthermore, muscle lactate content at 24 h postmortem alone accounted for a considerable portion of the variation in pork quality traits. Based on these results, the current study confirmed that the main factor influencing pork quality traits is the ultimate lactate content in muscle via postmortem glycolysis, and that levels of blood glucose and lactate at exsanguination and contents of muscle glycogen and lactate at postmortem can explain a large portion of the variation in pork quality even under the standard slaughter conditions.

Genomic characterization of the porcine CRTC3 and the effects of a non-synonymous mutation p.V515F on lean meat production and belly fat

cAMP-responsive element-binding protein (CREB)-regulated transcriptional coactivator 3 (CRTC3) is well known to be related to obesity in humans and mice. However, the effects of CRTC3 have not been studied in pigs. Here, we characterized the structure of the porcine CRTC3 gene and identified single nucleotide polymorphisms (SNPs) in its coding region. Moreover, mRNA expression profiles of CRTC3 in muscle and fat tissues were examined. Of the 40 identified SNPs, the p.V515F mutation, located on exon 16, was genotyped in 368 Yorkshire pigs. The p.V515F mutation was significantly associated with lean meat production ability, including reduced back fat thickness (P=0.0317) and loin eye area (P=0.0174). Moreover, the SNP was significantly associated with differences in intermuscular fat (P=0.0092), total muscle area in the belly (P=0.0108), and total fat percentage in the belly (P=0.0298). Taken together, our results suggest that the p.V515F mutation affects to lean meat production ability and amount of belly fat.