Seed Treatment with Illite Enhanced Yield and Nutritional Value of Soybean Sprouts.

Soybean sprouts, a nutritional food product, can contribute to food security because they can be grown within a week and do not require sophisticated technology. The yield and quality of soybean sprouts are influenced by various factors, including seed priming and growing conditions. The objective of this study was to investigate the effects of seed soaking in different concentrations of illite, a clay mineral, on the yield and quality of soybean sprouts. Soybean seeds soaked in five concentrations (0.5%, 1%, 3%, 5%, and 10%, w/v) of illite or tap water for 8 h were named IP-0.5, IP-1, IP3, IP-5, IP-10, and control, respectively. The highest sprout yield was found in IP-3, followed by IP-1, and IP-5, which had 11.1%, 8.8%, and 7.4% increments, respectively, compared to the control. The content of vitamin C, mineral element, isoflavone, total polyphenol, and total flavonoid was higher in many of the illite-treated soybean sprouts than in the control. The overall results indicated that pre-soaking soybean seeds in lower concentrations (0.5-3%, w/v) of illite could be helpful to enhance the yield and nutritional value of soybean sprouts in an easy and inexpensive way.

Barriers to initiating SGLT2 inhibitors in diabetic kidney disease: a real-world study.

BACKGROUND: Sodium-glucose cotransporter 2 inhibitor (SGLT2i) should be considered for patients with type 2 diabetes (T2D) and chronic kidney disease (CKD) having estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m2 and urine albumin-to-creatinine ratio (UACR) > 30 mg/g. However, SGLT2i is currently underprescribed among eligible, at-risk patients for CKD progression. We analyzed prescription patterns and barriers to initiating SGLT2i in patients with T2D and CKD in real practice. METHODS: A total of 3,703 consecutive outpatients with T2D from four teaching hospitals during six months (2019 ~ 2020) were reviewed. Five eGFR categories (G1, ≥ 90; G2, 60-89; G3ab, 30-59; G4-5, < 30 mL/min/1.73 m2) and three UACR categories (A1, < 30; A2, 30-300; A3, > 300 mg/g) were used to define CKD status. RESULTS: Overall, 25.8 % patients received SGLT2i in the following eGFR and albuminuria categories: G1 (A1, 31 %; A2, 48 %; A3, 45 %); G2 (A1, 18 %; A2, 24 %; A3, 30%); and G3 (A1, 9 %; A2, 7 %; A3, 13 %). Total prevalence estimate of CKD was 33.8 % (n = 1,253), of whom 25.6 % patients received SGLT2i. We defined eGFR ≥ 45 mL/min/1.73 m2 and UACR ≥ 30 mg/g as high-risk CKD group eligible for SGLT2i (n = 905), of whom 32.9 % patients were treated with an SGLT2i. In this high-risk group, SGLT2i initiation showed negative correlations with age ≥ 65 years and recent hospitalization. Conversely, HbA1c level, body mass index (BMI), presence of diabetic retinopathy, and previous heart failure events were positively correlated with SGLT2i initiation. CONCLUSIONS: Only 32.9 % of T2D with CKD eligible for SGLT2i is currently treated with SGLT2i in real-world clinical practice. The older patient group and clinical inertia are the main barriers to initiate SGLT2i for eligible patients. Clinicians should change the glucocentric approach and focus on reducing renal events in T2D.

Pu-erh Tea Extract Treatment Could Be an Efficient Way to Enhance the Yield and Nutritional Value of Soybean Sprout.

Soybean sprouts are one of the most inexpensive and nutritious food items that can be easily grown year-round. Several studies have been conducted to increase their yield and nutritional values. This study was carried out to examine the effects of Pu-erh tea extracts on the production and nutrients content of soybean sprouts. Soybean seeds were soaked in 1%, 2%, or 3% (w/v) tea extracts, or tap water, before keeping for sprout cultivation; the sprout samples were named PE-1, PE-2, PE-3, and the control, respectively. The sprout yields were increased by up to 17% in PE-2 and PE-3 than in the control. The vitamin C, total free amino acid, total mineral, total isoflavone, total polyphenol, and flavonoid contents as well as the antioxidant potentials of the tea extract-treated sprouts were higher than those of the control. The results indicated that pre-soaking soybean seeds in 2% Pu-erh tea extracts could offer an easy, inexpensive, and efficient way to improve the yield and nutritional value of soybean sprouts.

Comparative assessment regarding antioxidative and nutrition potential of Moringa oleifera leaves by bacterial fermentation.

Moringa is considered as a miraculous plant because of its outstanding health-promoting properties. Moringa leaves are used in various forms for various purposes owing to its potential against that purpose. This experiment was performed to utilize the hidden potential of Moringa leaves. The Moringa leaves were fermented by Bacillus subtilis KCTC 13,241 for 24, 48, 72 and 96 h to identify the best time duration of fermentation. The antioxidant potential of fermented Moringa leaves was estimated by measuring the total phenolic content (TPC), total isoflavones content (TIFC), DPPH and ABTS free radical scavenging activity and SOD-like activity. In addition to these parameters, the concentration of various total amino acids (TAA) and fatty acids were also determined. The best treatment was 48 h fermented Moringa leaves because of the best results in all measured parameters except in fatty acids concentration. The highest fatty acids concentration was recorded in 24 h fermented leaves. The results of 48 h fermented Moringa leaves regarding TAA, TPC, TIFC, DPPH and ABTS radical scavenging potential and SOD-like activity were 121.95 ± 3.74 mg/g, 310.25 ± 3.77 µg GAE/g, 1083.38 ± 5.92 µg/g, 63.12 ± 2.38%, 78.45 ± 3.32%, and 34.55 ± 1.05% respectively. The palmitic, stearic, oleic, linoleic and linolenic acid concentration in 24 h fermented Moringa leaves was 55.32 ± 1.93, 56.02 ± 2.12, 53.82 ± 2.54, 55.95 ± 1.62 and 56.41 ± 1.43% respectively. In conclusion, the present results disclose that fermented Moringa leaves are the source of natural antioxidants and nutrients.

The association of diabetes duration and glycemic control with depression in elderly men with type 2 diabetes mellitus.

BACKGROUND: The prevalence of depression and type 2 diabetes mellitus (T2DM) are increasing in the elderly and are reportedly related to each other. We evaluated the relationship between T2DM-related factors and the degree of depression in elderly patients with T2DM based on gender. MATERIALS AND METHODS: A total of 155 patients with T2DM (56 males and 99 females aged ≥ 65 years) from seven hospitals were included in the study. To assess the status of depressive symptoms, the short form of the Geriatric Depression Scale-Korean version (SGDS-K) was used. We evaluated DM-related factors, such as T2DM duration, hemoglobin A1c (HbA1c) levels, and T2DM complications, as well as other possible factors that could affect depression, such as cognitive function, physical function, education level, and other personal factors. RESULTS: Mean age of the participants was 71.3 years with a mean HbA1c level of 7.6%. Males in the good glycemic control group (HbA1c <7%) showed lower SGDS-K scores compared to those in the poor glycemic control group, and the mean SGDS-K score was higher in the group with a longer duration of DM (M10 years); however, no difference was observed in females. Males and females with microvascular and macrovascular complications tended to have higher SGDS-K scores than participants with no microvascular or macrovascular complications. A multiple linear regression analysis revealed that DM duration and HbA1c level were independently associated with SGDS-K scores in males. CONCLUSION: Greater depression was associated with poorer glycemic control and a longer duration of DM in elderly males with T2DM.

Comparison of antioxidants potential, metabolites, and nutritional profiles of Korean fermented soybean (Cheonggukjang) with Bacillus subtilis KCTC 13241.

This study was carried out to determine the effect of different concentrations of Bacillus subtilis (0, 1, 3, 5, and 7%) on the antioxidant potential and biochemical constituents of traditional Korean fermented soybean, Cheonggukjang (CKJ). The antioxidant capacity was studied using the reducing power, 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2-azinobis (3-ethyl-benzothiazoline-6-sulfonic acid) (ABTS) assays and the total phenolic contents (TPC) were measured using the Folin-Ciocalteu method. CKJ prepared using 1% B. subtilis revealed the highest TPC (5.99 mg/g), total amino acids (7.43 mg/g), DPPH (94.24%), and ABTS (86.03%) radical-scavenging activity and had the highest value of palmitic acid (11.65%), stearic acid (2.87%), and linolenic acid (11.76%). Results showed that the calcium, iron, sodium, and zinc contents increased in the CKJ prepared using 7% B. subtilis from 1481.38 to 1667.32, 41.38 to 317.00, 48.01 to 310.07, and 32.82 to 37.18 mg/kg respectively. In conclusion, the present results indicate that the fermentation of soybean with B. subtilis (KCTC 13241) significantly augments the nutritional and antioxidant potential of CKJ and it can be recommended as a health-promoting food source.

Persimmon Fruit Powder May Substitute Indolbi, a Synthetic Growth Regulator, in Soybean Sprout Cultivation.

Soybean sprouts are a major food item in Korea. Various studies have been carried out to enhance their yield and nutritional values. The objective of the present study was to examine the influence of persimmon fruit powder and Indolbi, a synthetic plant growth regulator, on the yield and nutritional value of soybean sprouts. Seeds were soaked in tap water containing 0.5%, 1.0%, 2.5% and 5.0% (w/v) persimmon fruit powder and the samples were named as PT-1, PT-2, PT-3, and PT-4, respectively. The yield increment was almost doubled in PT-3 and PT-4 than in the Indolbi treated sprouts on basis of the control. Vitamin C, isoflavones, and total phenolic contents as well as antioxidant potentials (determined by 1,1-diphenyl-2-picrylhydrazyl and superoxide anion radical scavenging assays) were also significantly (p < 0.05) higher in PT-3 compared to the Indolbi treatment and the control. However, total free amino acid and magnesium contents of Indolbi- applied sprouts were higher than in the fruit powder treatments. The overall results of the present study showed that persimmon fruit powder can be an option to enhance the yield and nutritional value of soybean sprouts since, due to potential health hazards, the use of synthetic chemicals like Indolbi is less preferred than the natural products.

Effects of Bacterial Fermentation on the Biochemical Constituents and Antioxidant Potential of Fermented and Unfermented Soybeans Using Probiotic Bacillus subtilis (KCTC 13241).

Fermented soybeans, cheonggukjang (CKJ), are considered to be more wholesome than soybeans in Korea. To select the best soybean cultivar for making functional CKJ, a comparison was made between the biological activities of four soybean cultivars in their unfermented soybean (UFS) and CKJ states. Changes in 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activity, 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) assays, superoxide dismutase (SOD)-like activity, total phenolic compounds, total amino acids, and isoflavones were investigated. The levels of DPPH, ABTS, SOD-like activity, and total phenolic compounds increased in CKJ among all cultivars. The isoflavone aglycone and total amino acids showed the highest amount in CKJ prepared from soybean cultivar Aga 3. These results suggest that the improved antioxidant activity of CKJ in all cultivars might occur because of the higher levels of aglycones and total phenolic compounds achieved during fermentation. Moreover, CKJ prepared from soybean cultivar Aga 3 showed higher antioxidant activity than the other cultivars and so can be considered for the commercial production of functional foods in the future.

In vitro synergistic anticancer activity of the combination of T-type calcium channel blocker and chemotherapeutic agent in A549 cells.

As a result of our continuous research, new 3,4-dihydroquinazoline derivative containing ureido group, KCP10043F was synthesized and evaluated for T-type Ca(2+) channel (Cav3.1) blockade, cytotoxicity, and cell cycle arrest against human non-small cell lung (A549) cells. KCP10043F showed both weaker T-type Ca(2+) channel blocking activity and less cytotoxicity against A549 cells than parent compound KYS05090S [4-(benzylcarbamoylmethyl)-3-(4-biphenylyl)-2-(N,N',N'-trimethyl-1,5-pentanediamino)-3,4-dihydroquinazoline 2 hydrochloride], but it exhibited more potent G1-phase arrest than KYS05090S in A549 cells. This was found to be accompanied by the downregulations of cyclin-dependent kinase (CDK) 2, CDK4, CDK6, cyclin D2, cyclin D3, and cyclin E at the protein levels. However, p27(KIP1) as a CDK inhibitor was gradually upregulated at the protein levels and increased recruitment to CDK2, CDK4 and CDK6 after KCP10043F treatment. Based on the strong G1-phase cell cycle arrest of KCP10043F in A549 cells, the combination of KCP10043F with etoposide (or cisplatin) resulted in a synergistic cell death (combination index=0.2-0.8) via the induction of apoptosis compared with either agent alone. Taken together with these overall results and the favorable in vitro ADME (absorption, distribution, metabolism, and excretion) profiles of KCP10043F, therefore, it could be used as a potential agent for the combination therapy on human lung cancer.

Unraveling the effect of structurally different classes of insecticide on germination and early plant growth of soybean [Glycine max (L.) Merr].

Although a considerable number of studies about the effect of different insecticides on plant physiology and metabolism have been carried out, research work about the comparative action of structurally different classes of insecticide on physiological and biochemical properties of soybean seed germination and early growth has not been found. The objective of this study was to investigate the effect of different classes of insecticides on soybean seed germination and early plant growth. Soybean seeds of Bosuk cultivar were soaked for 24h in distilled water or recommended dose (2mLL(-1), 1mLL(-1), 0.5gL(-1), and 0.5gL(-1) water for insecticides Mepthion, Myungtaja, Actara, and Stonate, respectively) of pesticide solutions of four structurally different classes of insecticides - Mepthion (fenitrothion; organophosphate), Myungtaja (etofenprox; pyrethroid), Actara (thiamethoxam; neonicotinoid), and Stonate (lambda-cyhalothrin cum thiamethoxam; pyrethroid cum neonicotinoid) - which are used for controlling stink bugs in soybean crop. Insecticides containing thiamethoxam and lamda-cyhalothrin cum thiamethoxam showed positive effects on seedling biomass and content of polyphenol and flavonoid, however fenitrothion insecticide reduced the seed germination, seed and seedling vigor, and polyphenol and flavonoid contents in soybean. Results of this study reveal that different classes of insecticide have differential influence on physiologic and metabolic actions like germination, early growth, and antioxidant activities of soybean and this implies that yield and nutrient content also might be affected with the application of different types of insecticide.

Biochemical Constituents and in Vitro Antioxidant and Anticholinesterase Potential of Seeds from Native Korean Persimmon Genotypes.

In the current study, the functional and biochemical potential of the seeds of four persimmon cultivars (PC1, PC2, PC3 and PC4) and their role against oxidative stress and acetylcholinesterase (AChE) inhibition were evaluated. In terms of biochemical compositions, free amino acids, fatty acids and organic acids analysis was performed. The free amino acids ranged from 2617.31 (PC2) to 3773.01 µg∙g(-1) dry weight (PC4). Oleic acid and linoleic acid were the principal fatty acids, which were significantly higher in PC4 and PC1, respectively. PC4 presented the highest amount of organic acid content (4212 mg∙kg(-1)), whereas PC2 presented the lowest (2498 mg∙kg(-1)). PC2 contained higher total phenolic content and flavonoid content, whereas PC3 had the lowest amount as compared to other cultivars. The in vitro DPPH, ABTS and superoxide anion radicals scavenging activity increased in a dose-dependent manner, whereas PC2 showed significantly higher scavenging activities as compared to PC1, PC2 and PC4 types. In the case of AChE inhibition, PC4 showed a moderate activity (67.34% ± 1.8%). In conclusion, the current findings reveal that the studied persimmon seeds cultivars are a source of bioactive natural antioxidants and AChE inhibitors. Such natural products could be employed in pharmaceutical and food industries, whilst can also be considered for the treatment of neurodegenerative diseases such as Alzheimer's.

Cetaceans evolution: insights from the genome sequences of common minke whales.

BACKGROUND: Whales have captivated the human imagination for millennia. These incredible cetaceans are the only mammals that have adapted to life in the open oceans and have been a source of human food, fuel and tools around the globe. The transition from land to water has led to various aquatic specializations related to hairless skin and ability to regulate their body temperature in cold water. RESULTS: We present four common minke whale (Balaenoptera acutorostrata) genomes with depth of ×13 ~ ×17 coverage and perform resequencing technology without a reference sequence. Our results indicated the time to the most recent common ancestors of common minke whales to be about 2.3574 (95% HPD, 1.1521 - 3.9212) million years ago. Further, we found that genes associated with epilation and tooth-development showed signatures of positive selection, supporting the morphological uniqueness of whales. CONCLUSIONS: This whole-genome sequencing offers a chance to better understand the evolutionary journey of one of the largest mammals on earth.

Multiple Genes Related to Muscle Identified through a Joint Analysis of a Two-stage Genome-wide Association Study for Racing Performance of 1,156 Thoroughbreds.

Thoroughbred, a relatively recent horse breed, is best known for its use in horse racing. Although myostatin (MSTN) variants have been reported to be highly associated with horse racing performance, the trait is more likely to be polygenic in nature. The purpose of this study was to identify genetic variants strongly associated with racing performance by using estimated breeding value (EBV) for race time as a phenotype. We conducted a two-stage genome-wide association study to search for genetic variants associated with the EBV. In the first stage of genome-wide association study, a relatively large number of markers (~54,000 single-nucleotide polymorphisms, SNPs) were evaluated in a small number of samples (240 horses). In the second stage, a relatively small number of markers identified to have large effects (170 SNPs) were evaluated in a much larger number of samples (1,156 horses). We also validated the SNPs related to MSTN known to have large effects on racing performance and found significant associations in the stage two analysis, but not in stage one. We identified 28 significant SNPs related to 17 genes. Among these, six genes have a function related to myogenesis and five genes are involved in muscle maintenance. To our knowledge, these genes are newly reported for the genetic association with racing performance of Thoroughbreds. It complements a recent horse genome-wide association studies of racing performance that identified other SNPs and genes as the most significant variants. These results will help to expand our knowledge of the polygenic nature of racing performance in Thoroughbreds.

Deleted copy number variation of Hanwoo and Holstein using next generation sequencing at the population level.

BACKGROUND: Copy number variation (CNV), a source of genetic diversity in mammals, has been shown to underlie biological functions related to production traits. Notwithstanding, there have been few studies conducted on CNVs using next generation sequencing at the population level. RESULTS: Illumina NGS data was obtained for ten Holsteins, a dairy cattle, and 22 Hanwoo, a beef cattle. The sequence data for each of the 32 animals varied from 13.58-fold to almost 20-fold coverage. We detected a total of 6,811 deleted CNVs across the analyzed individuals (average length = 2732.2 bp) corresponding to 0.74% of the cattle genome (18.6 Mbp of variable sequence). By examining the overlap between CNV deletion regions and genes, we selected 30 genes with the highest deletion scores. These genes were found to be related to the nervous system, more specifically with nervous transmission, neuron motion, and neurogenesis. We regarded these genes as having been effected by the domestication process. Further analysis of the CNV genotyping information revealed 94 putative selected CNVs and 954 breed-specific CNVs. CONCLUSIONS: This study provides useful information for assessing the impact of CNVs on cattle traits using NGS at the population level.

T-type Ca2+ channel blocker, KYS05090 induces autophagy and apoptosis in A549 cells through inhibiting glucose uptake.

It has been reported that [3-(1,1'-biphenyl-4-yl)-2-(1-methyl-5-dimethylamino-pentylamino)-3,4-dihydroquinazolin-4-yl]-N-benzylacetamide 2hydrochloride (KYS05090), a selective T-type Ca2+ channel blocker, reduces tumor volume and weight in the A549 xenograft model, but the molecular mechanism of cell death has not yet been elucidated. In this study, KYS05090 induced autophagy- and apoptosis-mediated cell death in human lung adenocarcinoma A549 cells. Although KYS05090 decreased intracellular Ca2+ levels, it was not directly related with KYS05090-induced cell death. In addition, KYS05090 generated intracellular reactive oxygen species (ROS) and reduced glucose uptake, and catalase and methyl pyruvate prevented KYS05090-induced cell death. These results indicate that KYS05090 can lead to autophagy and apoptosis in A549 cells through ROS generation by inhibiting glucose uptake. Our findings suggest that KYS05090 has potential chemotherapeutic value for the treatment of lung cancer.

Genome-wide Association Study of Integrated Meat Quality-related Traits of the Duroc Pig Breed.

The increasing importance of meat quality has implications for animal breeding programs. Research has revealed much about the genetic background of pigs, and many studies have revealed the importance of various genetic factors. Since meat quality is a complex trait which is affected by many factors, consideration of the overall phenotype is very useful to study meat quality. For integrating the phenotypes, we used principle component analysis (PCA). The significant SNPs refer to results of the GRAMMAR method against PC1, PC2 and PC3 of 14 meat quality traits of 181 Duroc pigs. The Genome-wide association study (GWAS) found 26 potential SNPs affecting various meat quality traits. The loci identified are located in or near 23 genes. The SNPs associated with meat quality are in or near five genes (ANK1, BMP6, SHH, PIP4K2A, and FOXN2) and have been reported previously. Twenty-five of the significant SNPs also located in meat quality-related QTL regions, these result supported the QTL effect indirectly. Each single gene typically affects multiple traits. Therefore, it is a useful approach to use integrated traits for the various traits at the same time. This innovative approach using integrated traits could be applied on other GWAS of complex-traits including meat-quality, and the results will contribute to improving meat-quality of pork.

Thoroughbred Horse Single Nucleotide Polymorphism and Expression Database: HSDB.

Genetics is important for breeding and selection of horses but there is a lack of well-established horse-related browsers or databases. In order to better understand horses, more variants and other integrated information are needed. Thus, we construct a horse genomic variants database including expression and other information. Horse Single Nucleotide Polymorphism and Expression Database (HSDB) (http://snugenome2.snu.ac.kr/HSDB) provides the number of unexplored genomic variants still remaining to be identified in the horse genome including rare variants by using population genome sequences of eighteen horses and RNA-seq of four horses. The identified single nucleotide polymorphisms (SNPs) were confirmed by comparing them with SNP chip data and variants of RNA-seq, which showed a concordance level of 99.02% and 96.6%, respectively. Moreover, the database provides the genomic variants with their corresponding transcriptional profiles from the same individuals to help understand the functional aspects of these variants. The database will contribute to genetic improvement and breeding strategies of Thoroughbreds.

Accurate estimation of effective population size in the korean dairy cattle based on linkage disequilibrium corrected by genomic relationship matrix.

Linkage disequilibrium between markers or genetic variants underlying interesting traits affects many genomic methodologies. In many genomic methodologies, the effective population size (Ne) is important to assess the genetic diversity of animal populations. In this study, dairy cattle were genotyped using the Illumina BovineHD Genotyping BeadChips for over 777,000 SNPs located across all autosomes, mitochondria and sex chromosomes, and 70,000 autosomal SNPs were selected randomly for the final analysis. We characterized more accurate linkage disequilibrium in a sample of 96 dairy cattle producing milk in Korea. Estimated linkage disequilibrium was relatively high between closely linked markers (>0.6 at 10 kb) and decreased with increasing distance. Using formulae that related the expected linkage disequilibrium to Ne, and assuming a constant actual population size, Ne was estimated to be approximately 122 in this population. Historical Ne, calculated assuming linear population growth, was suggestive of a rapid increase Ne over the past 10 generations, and increased slowly thereafter. Additionally, we corrected the genomic relationship structure per chromosome in calculating r(2) and estimated Ne. The observed Ne based on r(2) corrected by genomics relationship structure can be rationalized using current knowledge of the history of the dairy cattle breeds producing milk in Korea.

Genome-wide analysis of copy number variations reveals that aging processes influence body fat distribution in Korea Associated Resource (KARE) cohorts.

Many anthropometric measures, including body mass index (BMI), waist-to-hip ratio (WHR), and subcutaneous fat thickness, are used as indicators of nutritional status, fertility and predictors of future health outcomes. While BMI is currently the best available estimate of body adiposity, WHR and skinfold thickness at various sites (biceps, triceps, suprailiac, and subscapular) are used as indices of body fat distribution. Copy number variation (CNV) is an attractive emerging approach to the study of associations with various diseases. In this study, we investigated the dosage effect of genes in the CNV genome widely associated with fat distribution phenotypes in large cohorts. We used the Affymetrix genome-wide human SNP Array 5.0 data of 8,842 healthy unrelated adults in KARE cohorts and identified CNVs associated with BMI and fat distribution-related traits including WHR and subcutaneous skinfold thickness at suprailiac (SUP) and subscapular (SUB) sites. CNV segmentation of each chromosome was performed using Golden Helix SVS 7.0, and single regression analysis was used to identify CNVs associated with each phenotype. We found one CNV for BMI, 287 for WHR, 2,157 for SUP, and 2,102 for SUB at the 5% significance level after Holm-Bonferroni correction. Genes included in the CNV were used for the analysis of functional annotations using the Database for Annotation, Visualization and Integrated Discovery (DAVID v6.7b) tool. Functional gene classification analysis identified five significant gene clusters (metallothionein, ATP-binding proteins, ribosomal proteins, kinesin family members, and zinc finger proteins) for SUP, three (keratin-associated proteins, zinc finger proteins, keratins) for SUB, and one (protamines) for WHR. BMI was excluded from this analysis because the entire structure of no gene was identified in the CNV. Based on the analysis of genes enriched in the clusters, the fat distribution traits of KARE cohorts were related to the fat redistribution associated with the aging process. In addition to structural variation, dosage effect analysis of genes based on CNV is useful to gain an understanding of the comprehensive biological phenomena underlying particular phenotypes and/or diseases.

Genome-wide association study of copy number variations associated with pulmonary function measures in Korea Associated Resource (KARE) cohorts.

Copy number variation (CNV) is an attractive emerging approach to study the association with various diseases. We performed a CNV-based genome-wide association study of pulmonary function measures (FEV(1), FVC, and FEV(1)/FVC) in KARE cohorts. Affymetrix Genome-wide Human SNP Array 5.0 was used to measure genome-wide variation and CNV segmentation was performed using Golden Helix SVS 7.0. Single and multivariate regressions were used for the association study using the R statistical package and the Dabatase for Annotation, Visualization and Integrated (DAVID v6.7b) tool for the functional annotation. We identified significantly associated 1260 CNVs with pulmonary function measures of FEV(1) and FVC. Functional gene classification and annotation analysis found 5 highly enriched clusters, the BPI/LBP/Plunc superfamily, myosin, serpin peptidase inhibitor, protein tyrosine phosphatase, and olfactory receptors. According to the functional annotation, gene-based CNVs are likely to be involved in the pathogenesis and inflammatory responsiveness of pulmonary diseases.