Association of lipoprotein lipase (LPL) single nucleotide polymorphisms with type 2 diabetes mellitus

조윤신,고민진,한혜리,Seung-Hun Cha,Hung-Tae Kim,Haesook Min,신형두,Chan Park,Bok-Ghee Han,조남한,Chol Shin,Kuchan Kimm,오범석 생화학분자생물학회 2008 Experimental and molecular medicine Vol.40 No.5

The etiology and pathogenesis of type 2 diabetes mellitus (T2DM) are not completely understood although it is often associated with other conditions such as obesity, hypertension, and dyslipidemia. Lipoprotein lipase (LPL) is a key enzyme in human lipid metabolism that facilitates the removal of triglyceride-rich lipoproteins from the bloodstream. LPL hydrolyzes the core of triglyceride-rich lipoproteins (chylomicrons and very low density lipoprotein) into free fatty acids and monoacylglycerol. To gain insight into the possible role of LPL in T2DM, nine single nucleotide polymorphisms (SNPs) of LPL were analyzed for the association with T2DM using 944 unrelated Koreans, including 474 T2DM subjects and 470 normal healthy controls. Of the nine LPL SNPs we analyzed, a significant association with multiple tests by the false discovery rate (FDR) was observed between T2DM and SNP rs343 (+13836C>A in intron 3). SNP rs343 was also marginally associated with some of T2DM-related phenotypes including total cholesterol, high density lipoprotein cholesterol (HDLc), and log transformed glycosylated hemoglobin in 470 normal controls, although no significant association was detected by multiple tests. In total, our results suggest that the control of lipid level by LPL in the bloodstream might be an important factor in T2DM pathogenesis in the Korean population. The etiology and pathogenesis of type 2 diabetes mellitus (T2DM) are not completely understood although it is often associated with other conditions such as obesity, hypertension, and dyslipidemia. Lipoprotein lipase (LPL) is a key enzyme in human lipid metabolism that facilitates the removal of triglyceride-rich lipoproteins from the bloodstream. LPL hydrolyzes the core of triglyceride-rich lipoproteins (chylomicrons and very low density lipoprotein) into free fatty acids and monoacylglycerol. To gain insight into the possible role of LPL in T2DM, nine single nucleotide polymorphisms (SNPs) of LPL were analyzed for the association with T2DM using 944 unrelated Koreans, including 474 T2DM subjects and 470 normal healthy controls. Of the nine LPL SNPs we analyzed, a significant association with multiple tests by the false discovery rate (FDR) was observed between T2DM and SNP rs343 (+13836C>A in intron 3). SNP rs343 was also marginally associated with some of T2DM-related phenotypes including total cholesterol, high density lipoprotein cholesterol (HDLc), and log transformed glycosylated hemoglobin in 470 normal controls, although no significant association was detected by multiple tests. In total, our results suggest that the control of lipid level by LPL in the bloodstream might be an important factor in T2DM pathogenesis in the Korean population.

Identification of genetic loci stratified by diabetic status and microRNA related SNPs influencing kidney function in Korean populations

조윤신,임지선,고인송 한국유전학회 2016 Genes & Genomics Vol.38 No.7

Chronic kidney disease (CKD) is characterized by a progressive loss of kidney function over a period of months or years. It is estimated that about 7.2 % of adults over the age of 30 have CKD worldwide. Although one of the major risk factors of CKD is family history, the heritability of CKD is not fully understood. It is also known that the diabetic condition is highly influential on the onset of CKD. To understand the genetic bases of CKD that remain unidentified, we performed genetic association analyses for kidney function-related traits such as blood urea nitrogen (BUN) and albumin in subjects stratified by diabetic status. In the discovery stage of the study, we used genome-wide scan data and clinical data in about 8800 subjects from the Korean Association Resource (KARE) project. Health2 study data comprising about 1800 subjects were used for the replication stage. Our two stage association analyses demonstrated that the LOC105374266 locus (rs9820070) showed strong evidence of association with BUN (P = 8.47 9 10-14) in nondiabetic normal subjects (n = *4300). To extend our knowledge of the genetic determinants influencing kidney function, we also analyzed the association between kidney function-related traits and microRNA related variants. For this analysis, miRNA related SNPs were selected from KARE and Health2 cohort genotype data. Our study suggests the potential relevance of miRNA to the kidney function (miR-518b for BUN; miR-146a and miR-1295a for albumin) in Korean populations.

Replication of the Association of the 6q22.31c Locus near GJA1 with Pulse Rate in the Korean Population

김남희,조윤신,김영진,오지희 한국유전체학회 2012 Genomics & informatics Vol.10 No.2

Pulse rate is known to be related to diverse phenotypes, such as cardiovascular diseases, lifespan, arrhythmia, hypertension,lipids, diabetes, and menopause. We have reported two genomewide significant genetic loci responsible for the variation in pulse rate as a part of the Korea Association Resource (KARE) project, the genomewide association study (GWAS) that was conducted with 352,228 single nucleoride polymorphisms typed in 8,842 subjects in the Korean population. GJA1 was implied as a functionally causal gene for pulse rate from the KARE study, but lacked evidence of replication. To re-evaluate the association of a locus near GJA1 with pulse rate, we looked up this signal in another GWAS conducted in a Health Examinee-shared cohort of 3,703 samples. Not only we were able to confirm two pulse rate loci (1q32.2a near CD46 and 6q22.13c near LOCL644502) identified in the KARE GWAS, we also replicated a locus (6q22.31c) near GJA1 by the lookup in the Health Examinee GWAS. Considering that the GJA1-encoded protein is a major component of cardiac gap junctions, a functional study might be necessary to validate its genuine molecular biological role in the synchronized contraction of the heart.

Identification of genetic loci associated with abdominal visceral adiposity in Korean populations

홍진태,조윤신 한국유전학회 2017 Genes & Genomics Vol.39 No.5

Abdominal obesity is characterized by accumulation of subcutaneous and visceral fat in the abdomen and has been reported to be largely responsible for many metabolic and vascular diseases. Although substantial effort has been dedicated to identification of genetic factors associated with abdominal obesity, as measured by the waist-hip ratio and waist circumference, only a few studies have explored associations with visceral fat accumulation in the abdomen. Furthermore, genetic studies of abdominal visceral adiposity conducted in Asian ethnic groups are rare. To gain insight into the genetic basis for visceral adiposity in Asian subjects, we conducted genome-wide association analysis for a pool of 1594 Korean subjects. Abdominal visceral fat area was estimated by computed tomography. After adjustment for age, linear association analysis identified three loci showing suggestive evidence of association (P < 5 × 10−6) in ASIC2, SLC35F3, and 5q14.2. Stratification by sex revealed one female-specific locus (rs17104731) located near LINC01519 with a genome-wide significant association for visceral adiposity (P = 4.66 × 10−8). Since visceral fat has been suggested to influence metabolic traits, we analyzed associations of the loci identified in this study with metabolic indicators, such as glucose, insulin, and lipid levels, and markers of kidney function. A locus (rs6699737) in SLC35F3 showed a nominal association (P < 5 × 10−2) with alanine transaminase, aspartate transaminase, and fasting plasma insulin. In addition, the linear association test using genetic risk score demonstrated that visceral adiposity loci detected in this study had a cumulative effect on abdominal visceral fat area, waist-hip-ratio, total cholesterol, and low density lipoprotein cholesterol. In summary, this study reports new loci associated with visceral adiposity and provides evidence supporting involvement of these loci in several metabolic traits in Korean populations.

여자중학생 운동선수의 혈액세포와 혈중빈혈지표 비교연구

이하얀,신세훈,조윤신,김동희,장선웅,백종수,김민진,김회원,윤선미 한국스포츠리서치 2007 한국 스포츠 리서치 Vol.18 No.5

Identification of Causal and/or Rare Genetic Variants for Complex Traits by Targeted Resequencing in Population-based Cohorts

김윤경,홍창범,조윤신 한국유전체학회 2010 Genomics & informatics Vol.8 No.3

Genome-wide association studies (GWASs) have greatly contributed to the identification of common variants responsible for numerous complex traits. There are, however, unavoidable limitations in detecting causal and/or rare variants for traits in this approach, which depends on an LD-based tagging SNP microarray chip. In an effort to detect potential casual and/or rare variants for complex traits, such as type 2 diabetes (T2D) and triglycerides (TGs), we conducted a targeted resequencing of loci identified by the Korea Association REsource (KARE) GWAS. The target regions for resequencing comprised whole exons, exon-intron boundaries, and regulatory regions of genes that appeared within 1 Mb of the GWA signal boundary. From 124 individuals selected in population-based cohorts, a total of 0.7 Mb target regions were captured by the NimbleGen sequence capture 385K array. Subsequent sequencing, carried out by the Roche 454 Genome Sequencer FLX, generated about 110,000 sequence reads per individual. Mapping of sequence reads to the human reference genome was performed using the SSAHA2 program. An average of 62.2% of total reads was mapped to targets with an average 22X-fold coverage. A total of 5,983 SNPs (average 846 SNPs per individual) were called and annotated by GATK software, with 96.5% accuracy that was estimated by comparison with Affymetrix 5.0 genotyped data in identical individuals. About 51% of total SNPs were singletons that can be considered possible rare variants in the population. Among SNPs that appeared in exons, which occupies about 20% of total SNPs, 304 nonsynonymous singletons were tested with Polyphen to predict the protein damage caused by mutation. In total, we were able to detect 9 and 6 potentially functional rare SNPs for T2D and triglycerides, respectively, evoking a further step of replication genotyping in independent populations to prove their bona fide relevance to traits.

퓨처리즘을 활용한 홈인테리어용 텍스타일제품디자인 사례연구

엄경희(Kyoung Hee Eom),조윤신(Yun Shin Cho) 한국디자인문화학회 2007 한국디자인문화학회지 Vol.13 No.4

평판형 전극으로 구성된 유전체 배리어 방전 반응기를 이용한 톨루엔 저감 특성

박재홍(Jae-Hong Park),조윤신(Yoon-Shin Jo),윤기영(Ki-Young Yoon),변정훈(Jeong-Hoon Byeon),황정호(Jungho Hwang) 한국대기환경학회 2008 한국대기환경학회지 Vol.24 No.6

비만 프로그램이 비만 중년 여성의 동맥경화지수와 HOMA Index에 미치는 영향

이하얀(Lee Ha-Yan),조윤신(Cho Yoon-Shin),김동희(Kim Dong-Hee),김석환(Kim Seok-Hwan) 한국체육과학회 2010 한국체육과학회지 Vol.19 No.1

The number of obese people has been steadily rising over one and a half times since recent ten years ago in Korea. Obesity accompanied by increased body fat could lead to hyperlipidemia, hyperinsulinemia, and hypertension, which are related to metabolic syndrome. With awareness of risks of obesity, the study of metabolic syndrome-related blood lipids predisposing to atherosclerosis have taken attention more. The purpose of this study is to investigate the effect of obesity program on AI and HOMA index in middle aged obese women. Middle aged obese women were recruited and exercised power walking, treadmill jogging for aerobic exercise(50-60%VO2max for first 1-6 weeks, 60-70%VO2max for later 7-12 weeks), weight training for resistant exercise(50-60%1RM for first 1-6 weeks, 60%-80%1RM for later 7-12 weeks), and Yoga training for a hour per exercise. AI and HOMA Index extrapolated from drawn blood sample at the beginning of exercise, 6 weeks after beginning exercise, and 12 weeks after beginning exercise were analysed. The variables were analyzed using repeated one-way ANOVA and Duncan post-hoc test. In the AI analysis, (TC-HDL-C)/HDL-C, TC/HDL-C, LDL-C/HDL-C decreased at 6 week and 12 week after beginning exercise, but not significantly. And the blood sugar, insulin, and HOMA Index did not show statistically significant change. As a result, we have found that obesity program comprised of several exercise types could affect positively to AI and would be beneficial to preventing and arteriosclerosis. However, further studies are necessary to connect various exercise types and the duration of exercise program with effects on prevention of atherosclerosis as well as to clear the relationship between the initial state of insulin resistance and the positive effects of exercise on the improvement of insulin resistance.

A Genome-wide Association Study of Copy Number Variation in Hematological Parameters in the Korean Population

김가경,조남훈,신철,조윤신,김종원 한국유전체학회 2010 Genomics & informatics Vol.8 No.3

Abnormal hematological values are associated with various disorders including cancer and cardiovascular, metabolic, infectious, and immune diseases. We report the copy number variations (CNVs) in clinically relevant hematological parameters, including hemoglobin level, red and white blood cell counts, platelet counts, and red blood cell (RBC) volume. We describe CNVs in several loci associated with these hematological parameters in 8,842 samples from Korean population-based studies. The data that we evaluated included four RBC parameters, one platelet parameter, and one associated with total white blood cell (WBC) count, exceeding the genome-wide significance. We show that CNVs in hematological parameters are associated with some loci, different from previously associated loci reported in single nucleotide polymorphism (SNP) association studies.