Novel association between <i>CDKAL1</i> and cholesterol efflux capacity: Replication after GWAS-based discovery

Cheon, Eun Jeong,Cha, Do Hyeon,Cho, Sung Kweon,Noh, Hye-Min,Park, Sungha,Kang, Seok-Min,Gee, Heon Yung,Lee, Sang-Hak Elsevier 2018 Atherosclerosis Vol.273 No.-

<P><B>Abstract</B></P> <P><B>Background and aims</B></P> <P>Although the importance of the functional properties of high-density lipoprotein (HDL) has been increasingly emphasized, studies on the genetic factors associated with HDL function are highly limited. The aim of this study was to identify genetic variants associated with an individual's cholesterol efflux capacity (CEC) using a genome-wide association study approach.</P> <P><B>Methods</B></P> <P>This study included a discovery group of 607 subjects with coronary artery disease and an independent replication group of 158 subjects. CEC was assessed using a radioisotope and ApoB-depleted serum. Genome-wide associations between the adjusted CEC and genotyped and imputed variants were examined with linear regression, assuming an additive genetic model. Finally, adjustments were made for confounding parameters to assess the independence of associations and to determine R<SUP>2</SUP> of overall model on CEC.</P> <P><B>Results</B></P> <P>In the discovery group, 631 variants showed significant association with CEC, and five of them were found to correlate with CEC in the replication group. One of them was located near <I>LOC541471</I> in 2q13, whereas the other four (rs117835232, rs117252933, rs118064592, and rs150434350) were located in <I>CDKAL1</I> in 6p22.3. The association between the presence of any <I>CDKAL1</I> variant and CEC was significant after adjustment for clinical and laboratory variables. High-density lipoprotein-cholesterol levels also showed a very significant association with CEC. Body mass index, current alcohol use, triglycerides levels, low-density lipoprotein-cholesterol levels and statin use showed borderline associations with CEC.</P> <P><B>Conclusions</B></P> <P>We identified and replicated genetic variants associated with CEC using a genome-wide association study-based approach. <I>CDKAL1</I> variants showed correlations with CEC independent of HDL-cholesterol levels and other clinical characteristics.</P> <P><B>Highlights</B></P> <P> <UL> <LI> We identified and replicated genetic variants associated with cholesterol efflux capacity (CEC). </LI> <LI> One variant was located near <I>LOC541471</I> on 2q13, and four were in <I>CDKAL1</I> on 6p22.3 </LI> <LI> The association between any <I>CDKAL1</I> variant and CEC was significant after adjustment. </LI> </UL> </P>

경피적 골생검 : 정확도, 효율적 정확도 및 진단적 유용도 Accuracy, Effective Accuracy, and Diagnostic Utility

천병국,허진도,김종민,오경승,정규식,조영덕 高神大學 醫學部 1996 高神大學醫學部 論文集 Vol.11 No.1-2

경피적 골생검 : 정확도, 효율적 정확도 및 진단적 유용도 Accuracy, Effective Accuracy, and Diagnostic Utility

천병국,허진도,김종민,오경승,정규식,조영덕 고신대학교 의학부 1996 高神大學校 醫學部 論文集 Vol.11 No.1-2

목적 : 골질환의 종류에 따라 경피적 골생검이 정확도와 임상적인 유용성에 있어서 어떠한 차이를 보이는가를 알아보고자 하였다. 대상 및 방법 : 1988년 2월부터 1993년 9월까지 경피적 골생검을 시행한 106예를 대상으로, 추정진단에 따라 전이성 골종양, 골감염, 원발성 골종양, 기타병변으로 분류하였으며 이의 (1)정확도(Accuracy), (2)효율적 정확도(Effective accuracy) 및 (3)진단적 유용도(Diagnostic utility)를 후향적으로 비교 분석하였다. 결과 : 106예의 경피적 골생검의 추정진단에 따른 정확도는 전이성 골종양(84%). 골감염(87%), 원발성 골종양(85%)에서 비슷했다. 효율적 정확도는 전이성 골종양(79%)이 가장 높았으며, 골감염(73%)은 전체평균과 비슷했고, 원발성 골종양(59%)이 가장 낮았다. 진단적 유용도는 전이성 골종양(58%)이 가장 높았고, 골감염(47%)에 이어 원발성 골종양(19%)이 가장 낮았다. 결론 : 전이성 골종양이나 감염성 골질환이 의심되는 경우 경피적 골생검은 정확도가 높을 뿐 아니라 임상적으로 유용한 검사법이다. 하지만 원발성 골종양이 의심되는 경우는 전이성 골종양이나 감염성 골질환에 비해 정확도는 비슷하였으나 임상적인 유용성에는 한계가 있음을 알 수 있었다. Purpose : Percutaneous needle biopsy (PCNB) of bone lesions is relatively safe procedure that often provides critical information for patient management. We undertook this study to determine which bone lesions would be most and least clinically valuable for PCNB. Materials and methods : We retrospectively reviewed the results of 106 PCNBs of 102 patients with bone lesions to determine the accuracy, effective accuracy, and diagnostic utility of PCNB of bone lesions in various clinical settings. Results: The accuracy was similar in various clinical settings compared with overall cases (86%); suspected metastatic lesions (84%), suspected bone infections (87%).and primary bone tumors (85%). Compared with effective accuracy of overall cases (71%), accuracy was higher in suspected metastatic lesions (79%), roughly equal in suspected infections (73%), and lower in suspected primary tumors (59%). Diagnostic utility in suspected metastatic lesions (58%) washigher than overall cases (42%), slightly higher in bone infections (47%), and lower in primary bone tumors (19%). Conclusion : PCNB provided more useful information in the settings of suspected metastatic diseases or suspected bone infections. But in suspected primary bone tumors it should be done with knowledge that the results of PCNB may have limited clinical value although it is accurate.

강교제작구조전개 및 생산정보 추출기술 개발

박천종(Cheon Jong Park),김성민(Seong Min Kim),설가영(Ga Yung Seol) 한국강구조학회 2022 韓國鋼構造學會誌 Vol.34 No.6

Ovarian Cycle, the Biological Minimum Size and Artificial Spawning Frequency in Female Meretrix petechialis (Bivalvia: Veneridae) in Western Korea

Je-Cheon Jun,Yong Min Kim,정재승,Ee-Yung Chung,이기영 한국발생생물학회 2012 발생과 생식 Vol.16 No.3

The ovarian cycle, the biological minimum size, and artificial spawning frequency by artificial spawning induction of the female hard clam, Meretrix petichialis, were investigated by histological observations and morphometric data. The ovarian cycle of this species can be classified into five successive stages: early active stage, late active stage,ripe stage, partially spawned stage, and spent/inactive stage. The spawning period was from June to September, and the main spawning occurred between July and August when the seawater temperature exceeds over 20℃. The biological minimum size (shell length at 50% of first sexual maturity) in females were 40.39 mm in shell length (considered to be two years of age), and all clams over 50.1 mm in shell length sexually matured. In this study, the mean number of the spawned eggs by spawning induction increased with the increase of size (shell length) classes. In case of artificial spawning induction for the clams > 40.39 mm, the number of spawned eggs from the clams of a sized class was gradually decreased with the increase of the number of the spawning frequencies (the first, second, and third spawning). In the experiments of artificial spawning induction during the spawning season, the interval of each spawning of this species was estimated to be 15-18 days (approximately 17 days).

Ovarian Cycle, the Biological Minimum Size and Artificial Spawning Frequency in Female Meretrix petechialis (Bivalvia: Veneridae) in Western Korea

Jun Je-Cheon,Kim Yong-Min,Chung Jae-Seung,Chung Ee-Yung,Lee Ki-Young 한국발생생물학회 2012 발생과 생식 Vol.16 No.3

The ovarian cycle, the biological minimum size, and artificial spawning frequency by artificial spawning induction of the female hard clam, Meretrix petechialis, were investigated by histological observations and morphometric data. The ovarian cycle of this species can be classified into five successive stages: early active stage, late active stage, ripe stage, partially spawned stage, and spent/inactive stage. The spawning period was from June to September, and the main spawning occurred between July and August when the seawater temperature exceeds over . The biological minimum size (shell length at 50% of first sexual maturity) in females were 40.39 mm in shell length (considered to be two years of age), and all clams over 50.1 mm in shell length sexually matured. In this study, the mean number of the spawned eggs by spawning induction increased with the increase of size (shell length) classes. In case of artificial spawning induction for the clams > 40.39 mm, the number of spawned eggs from the clams of a sized class was gradually decreased with the increase of the number of the spawning frequencies (the first, second, and third spawning). In the experiments of artificial spawning induction during the spawning season, the interval of each spawning of this species was estimated to be 15-18 days (approximately 17 days).

Lipopolysaccaride로 유도된 Raw 264.7 세포에서 큰열매모자반 에탄올 추출물의 항염증 활성

천지민(Ji Min Cheon),김향숙(Hyang Suk Kim),최은옥(Eun Ok Choi),권다혜(Da Hye Kwon),최영현(Yung Hyun Choi),김병우(Byung Woo Kim),황혜진(Hye Jin Hwang) 한국생명과학회 2017 생명과학회지 Vol.27 No.12

본 연구에서는 갈조류인 큰열매모자반 에탄올 추출물(Ethanol extract of Sargassum Macrocarpum, EESM)의 항염증 활성을 조사하였다. Lipopolysaccharide (LPS)로 염증이 유도된 RAW 264.7 대식세포에서 EESM에 의한 항염증 효과를 조사한 결과 EESM은 nitric oxide (NO)와 prostaglandin E2 (PGE2)의 분비를 억제하는 결과를 보였고, 이는 inducible NO synthase (iNOS)와 cyclooxygenase-2 (COX-2)의 발현 역시 억제하였다. 또한 전염증성 사이토카인인 tumor necrosis factor-alpha (TNF-α)와 interleukin 1 beta (IL-1β)의 발현도 억제하였다. 이러한 염증반응이 어떤 신호경로를 통해 일어나는지 알아보기 위해 nuclear factor kappa B (NF-ĸB), phosphoinositide-3-kinase (PI3K)/Akt 그리고 mitogen-activated protein kinases (MAPKs) 신호전달 경로를 조사한 결과 EESM에 의해 NF-ĸB가 세포질에서 핵으로 이동과 Akt 단백질의 인산화가 억제되었고 MAPK에 속하는 kinase 중 ERK의 단백질 인산화가 억제되었다. 따라서 EESM이 NF-ĸB 신호계를 포함한 PI3K/Akt 및 MAPK/ERK 신호경로를 동시에 관여하고 있음을 알 수 있었다. 또한 heme oxygenase-1 (HO-1)과 그 전사 인자인 nuclear factor-E2-related factor 2 (Nrf2)의 단백질 발현에 미치는 영향을 분석한 결과 EESM에 의해 HO-1 및 Nrf2의 발현이 증가됨을 보였다. 본 연구 결과 EESM은 높은 항염증 활성을 갖는 것으로 확인되였으며 향후 잠재적인 기능성 소재로서 유용하게 활용될 수 있을 것으로 사료된다. Sargassum macrocarpum is a widely distributed marine brown algae found in the North Pacific. The objective of this study was to evaluate the anti-inflammatory activity of an ethanol extract of S. macrocarpum (EESM). First, we investigated the anti-inflammatory activities of EESM in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. EESM treatment suppressed nitric oxide (NO) and prostaglandin E2 (PGE2) production and inhibited the expressions of the inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at the mRNA and protein levels. In addition, the expression of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin-1 beta (IL-1β), was decreased in a dose dependent manner. Investigation of the signaling pathways of nuclear factor kappa B (NF-ĸB), phosphoinositide-3-kinase (PI3K)/Akt, and mitogen-activated protein kinases (MAPKs) revealed suppression of NF-ĸB translocation from the cytosol to nucleus by EESM treatment. The phosphorylation of the Akt and ERK proteins was also inhibited by EESM treatment. EESM treatment also stimulated the expression of the heme oxygenase-1 (HO-1) enzyme and its upstream transcription factor, nuclear factor-E2-related factor 2 (Nrf2). These results suggest that EESM has anti-inflammatory activity and could have potential uses in the field of nutraceuticals.

프리팹강구조의 LRFD(한계상태설계법) 기반 설계 툴 및 제작 구조전개 자동화 기술 개발

박천종(Park, Cheon Jong),김성민(Kim, Seong Min),설가영(Seol, Ga Yung) 한국강구조학회 2023 한국강구조학회 학술대회 발표집 Vol.34 No.6

비타민과 불포화지방산, 그리고 피크노제놀을 함유한 복합제제의 주름 완화 및 자외선에 의한 색소침착 개선 효과

장민열(Chang,Min-Youl),박상기(Park Sang-Ki),곽택종(Kwak Taek-Jong),박형국(Park Hyoung-Kook),이천구(Lee Cheon-Koo),이헌식(Lee Heon-Sik),이선영(Ly Sun Yung),김성진(Kim Seong-Jin) 韓國營養學會 2009 Journal of Nutrition and Health Vol.42 No.6

총 108명의 피시험 자원자들을 대상으로 각각 54명씩 두 군으로 무작위 배정한 후 12주 동안 시험제제를 섭취 시키고 피부 색조도와 주름 정도, 혈청 내 α-tocopherol의 변화를 이중맹검법으로 평가한 결과 다음과 같은 결론을 얻었다. 1) 12주 동안의 시험제제 섭취 성실성 (순응도)에 대한 익명의 자가응답조사 결과, 응답에 응한 피시험 자원자 45명 중 31명이 90~100%, 14명이 70~80%의 비율로 시험 제제를 섭취하였다고 응답하여, 순응도는 만족할 만한 수준 이었다. 2) 대조군 (가나다 군)은 남자 22명, 여자 32명으로서 평균 연령 22.8 ± 3.0세였으며, 시험군 (ABC 군)은 남자 25명, 여자 29명으로서 평균 연령 23.0 ± 3.4세로 군간 차이가 없었다. 그 외 시험시작전 군별 최소홍반량, 자외선 조사 전후의 피부 색조도는 모두 동일한 수준으로 평가되었다. 3) 상완부 내측 피부에 자외선으로 유도한 인공 색소 침착 후 미백 효과를 측정한 색차계 L값의 변화도 (ΔL값)는 12주째에 시험군 (ΔL = 3.817 ± 2.228)에서 대조군 (ΔL = 2.731 ± 2.138)보다 유의하게 높았다 (p = 0.011). 4) 안면부 안와 주위 주름을 대상으로 모사판을 획득하고 영상 분석한 음영 비율을 주름 완화 유효 백분율로 비교한 결과, 8주, 12주에 시험군에서 대조군보다 유의한 증가를 나타내었다 (p = 0.0217, p = 5.317E-06). 5) 혈청 내 유효성분 vitamin E (α-tocopherol) 농도의 정량적 변동을 시험제제 섭취 전과 섭취 12 후에 측정한 결과, 시험군에서 대조군보다 유의하게 증가하였다 (p = 0.0001). 6) 시험제제를 12주간 섭취한 후 측정한 결과들을 종합하여 볼 때 ABC 군이 가나다 군에 비해 피부의 미백 및 주름 완화 효과가 유의하게 높은 것을 알 수 있었는데, ABC군이 LGNC-5를 유효 성분으로 함유한 시험제제를 섭취한 군이었다. In this study, the effects of a mixture consisting of vitamin E, vitamin C, pycnogenol and evening primrose oil (mixture LGNC-5) on ultraviolet light (UV) induced pigmentation and wrinkle reductions of normal healthy volunteers were studied. In a double-blind placebo-controlled study, each of 54 subjects took daily either 4 capsules of the mixture LGNC-5 (Group ABC; 282.5 ㎎/capsule) or placebo (Group Ganada). We irradiated 2.5 MED UV on the upper arms and measured the whitening effect by colorimeter-based L value. The level of wrinkle reduction was determined by image analysis using skin replica around the crow’ feet, and the level of serum vitamin E was determined at baseline and 12 weeks. After 12-week oral administration, the treated group showed a significant reduction in skin pigmentation and wrinkles compared with the placebo group (p = 0.011 and p = 0.000005 , respectively). Also, the level of serum vitamin E was significantly increased in the treated group after 12-week oral adminstration of the mixture compared with that in the placebo group (p = 0.0001). In conclusion, 12-week oral administration of LGNC-5 as a dietary supplement could be effective to reduce both UV induced pigmentation and skin wrinkle without side effects.

랫드 발꿈치힘줄에 분포하는 CGRP신경섬유의 기원에 관한 연구

김철민(Cheol Min Kim),박용욱(Yong-Wook Park),유정한(Jung Han Yoo),이지동(Ji Dong Lee),강태천(Tae-Cheon Kang),박승국(Seung-Kook Park),원무호(Moo Ho Won),정영기(Yung Khee Chung) 대한해부학회 2002 Anatomy & Cell Biology Vol.35 No.3

본 연구는 랫드 발꿈치힘줄 (calcaneal tendon)에 분포하는 CGRP 신경세포의 분포를 확인하기 위해 반대방향 이동추적 및 면역조직화학 염색을 수행한 결과 다음과 같은 결론을 얻었다. 발꿈치힘줄에 horseradish peroxidase (HRP) 또는 fluoro-gold (FG)를 주입한 경우 표지된 신경절세포들은 같은쪽 척수신경절에서만 관찰되었으며, 반대측에서는 관찰되지 않았다. 즉, 신경추적물질에 표지된 신경절세포들은 첫째허리분절 (L1)에서 첫째엉치분절 (S1) 척수신경절 내에 위치하였으며, 이 중 L6 척수신경절 내에 가장 많은 수의 세포가 분포하고 있었다. L1에서 S1까지의 척수신경절 내에는 CGRP세포들이 다수 분포하고 있었으나, 각각의 척수신경절 내에서 CGRP세포 분포는 유의한 차이를 나타내지 않았다. 신경추적물질이 표지된 신경절세포들 중 CGRP세포(FG±CGRP신경절세포)를 확인한 결과, 이 FG±CGRP세포들은 L3~L6 신경절에서만 관찰되었는데, 특히 L6 척수신경절 내에서 가장 많이 관찰되었다. 이상의 연구 결과는 발꿈치힘줄에 분포하는 신경섬유는 그 기원 및 CGRP 함유 정도에 차이가 있으며, 이러한 차이는 근육이나 힘줄의 이상시 진단이나 치료 등에 기초자료를 제공할 수 있을 것으로 생각된다. This study was performed to investigate origins of the dorsal root ganglion cells containing calcitonin gene-related peptide (CGRP) which innervate the calcaneal tendon in the rat. We used the horseradish peroxidase (HRP) or fluorogold (FG) to trace retrogradely somatic afferents in dorsal root ganglion cells after unilateral injections into the rat calcaneal tendon. HRP or fluoro-gold labeled DRG cells for the calcaneal tendon were seen generaaly in lumbosacral (L1 to S1) DRGs ipsilaterally. In lumbosacral DRGs, the largest number of labeled cells were found in the L6 DRG. Many DRG cell bodies contained the CGRP throughout the L1~S1. A plenty of HRP- or FG-labeled cells innervating the calcaneal tendon were also identified to contain the CGRP in L1~S1 DRGs. These FG±CGRP DRG cells innervating the calcaneal tendon were primarily found in the L6 DRG. These results suggest that the main sensory DRG for the calcaneal tendon is the L6. This fact may be available in diagnosis and treatment of neurogenic pain in the calcaneal tendon.