Polymorphism of the Interlekin-6 Gene Are Associated with Bone Mineral Density in Korean Menopausal Women

골다공증은 특히 여성에게 중요한 질환으로 평생 이환될 위험이 40-50%이다. 골다공증에 관련된 유전자를 찾으려는 연구가 vitamin D 수용체, 에스트로겐 수용체, Collagen-I-α-1 유전자 및 골단백질, 호르몬, 사이토카인에 대해 이루어지고 있다. Interleukin-6(IL-6)는 면역 반응과 조혈 작용에서 뿐 아니라 골 흡수를 조절하는데 있어서도 필수적인 사이토카인으로 IL-6 전사조절부위(promotor)의 다형성이 IL-6의 dysregulation과 이에 의한 만성 질환과 연관성이 있다. 이에 본 연구에서는 IL-6의 전사조절부위 중-572의 단일염기서열다형성(single nucleotide polymorphism; SNP)과 골밀도를 조사하여 그 상관관계를 규명하고자 하였고 다음과 같은 결과를 얻었다. 1. 폐경 여성 274명을 대상으로 하였고, 연구대상의 평균 나이는 52.7±9.2세, 평균 신장은 155.3±5.0cm, 평균 체중은 56.7±7.6kg, 평균 Body mass index(BMI)는 23.4±3.6kg/㎡이었으며 IL-6 유전자의 -572(G C)의 SNP type에 따른 차이는 없었다. 2. IL-6의 전자조절부위의 -572의 SNP는 GG군이 153명(55.6%), GC군이 107명(39.1%), CC군이 14명(5.3%)으로 나타났다. 3. IL-6 genotype에 따른 호르몬 대체요법 전의 요추(L2-L4)의 골밀도는 GG군; 1.03±0.17, GC군; 1.04±0.18, CC군; 1.00±0.17 g/㎠, 요추의 T-score는 GG군; -0.84±1.40, GC군; -0.70±1.46, CC군; -0.96±1.66으로 genotype간의 골밀도의 차이는 없었다. 대퇴골 경부의 골밀도는 GG군; 0.83±0.19, GC군; 0.85±0.19, CC군; 0.76±0.09 g/㎠으로 CC군이 다른 genotype에 비하여 낮은 골밀도를 보였으나 통계적으로 유의한 차이는 없었고, 대퇴골 경부의 T-score는 GG군; -0.67±1.17, GC군; -0.35±1.34, CC군; -1.31±0.89로 CC genotype에서 GC군에 비하여 통계적으로 유의하게 낮은 T-score를 보였다.(p<0.05) 4. IL-6 genotype에 따른 호르몬 대체요법 1년 후의 요추 골밀도는 GG군; 1.06±0.16, GC군; 1.09±0.12, CC군; 1.01±0.20 g/㎠, 요추 T-score는 GG군; -0.61±1.36, GC군; -0.37±1.00, CC군; -1.08±1.53으로 genotype간의 골밀도의 차이는 없었다. 대퇴골 경부의 골밀도는 GG군; 0.85±0.13, GC군; 0.90±0.13, CC군; 0.83±0.13 g/㎠으로 CC군이 다른 genotype에 비하여 낮은 골밀도를 보였으나 통계적으로 유의한 차이는 없었으며, 대퇴골 경부의 T-score는 GG군; -0.62±1.07, GC군; -0.16±1.07, CC군; -1.17±0.89로 CC군에서 GC군에 비하여 통계적으로 유의하게 낮은 T-score를 보였다.(p<0.05) 이상의 결과로 볼 때, 폐경 여성의 IL-6의 전사조절부위의 -572의 genotype이 CC 동형접합인 경우 대퇴골의 골밀도가 낮은 것으로 나타나 IL-6 전사조절부위의 유전자 다형성이 전사를 조절함으로써 골 흡수에 관여하여 폐경 후 골다공증의 유전적 소인이 될 것으로 사료된다. 이러한 IL-6의 전사조절부위 SNP와 폐경 후 골다공증에 관한 연구는 아직 한국인 여성에서는 보고 된 바 없어 한국인 여성의 골다공증의 유전적 소인에 관한 연구에 중요한 자료가 될 것이다.;Primary osteoporosis is a major public health problem, particularly for women, who have a 40-50% lifetime risk of osteoporosis. Because both peak bone mass and age-related bone loss are under multiple environmental and genetic influences, attention has recently turned toward identifying polymorphic gene markers for osteoporosis with BMD. Among the multiple candidate genes investigated, vitamin D receptor, estrogen receptor, and type I collagen alleles are actively studied by many investigators. And other bone proteins, hormone and cytokines are investigated, too. Interleukin-6 is a mutifunctional cytokine essential to the regulation of bone resorption, as well as the immune response and hematopoiesis. IL-6 and its receptor stimulate osteoclast development and, thereby, the process of bone resorption, they are pathogenic factors in bone loss, especially that triggered by an estrogen-deficiency state. Recently, a novel, functional G→C polymorphism at position -174 in the IL-6 gene promoter has been described. To investigate a possible relationship between single nucleotide polymorphism of human IL-6 promoter -572 locus and osteoporosis, we determined the genotypes of a large panel of Korean women at this polymorphic locus, and correlated their genotypes with bone mineral density. The results obtained were as follows; 1. The mean age, height, weight and BMI of patients were respectively 52.7±9.2 years, 155.3±5.0 cm, 56.7±7.6 kg and 23.4±3.6 kg/㎡. They were not significantly different. (p > 0.05) 2. The genotype distribution was as follows; GG genotype, 153(55.6%) women; GC genotype, 107(39.1%) women; CC genotype, 14(5.3%) women. 3. BMDs of pretreatment status, of lumbar spine in genotype GG, GC, CC were 1.03±O.17 g/㎠, 1.04±0.18 g/㎠, 1.00±0.17 g/㎠, respectively They were not significantly different(p > 0.05). BMDS of femur neck were -0.84±1.40 g/㎠, -0.70±1.43 g/㎠, -0.96±1.66 g/㎠, respectively. There was no statical significance in BMD in each genotypes(p > 0.05). 4. After 1 year of HRT treatment, there was no statistical significance in BMD in each genotypes(p > 0.05). 5. Among the BMD of each genotypes, T-score of femur neck was significantly higher in pretreatment GC genotype than pretreatment CC genotype(p < 0.05) and higher in post-1-year HRT-GC genotype than CC genotype. From the above results, we concluded that IL-6 -572 SNP have a correlation with BMD of postmenopausal Korean women. The BMD of CC genotype was significantly lower than BMD of other genotypes. IL-6 promoter -572 SNP would be a genetic factor of postmenopausal osteoporosis. Because there was no report about correlation between l1-6-572 SNP and postmenopausal osteoporosis in Korea, this study will bea important data for further investigations.논문개요 = ⅵ Ⅰ. 서론 = 1 Ⅱ. 연구 대상 및 방법 = 4 Ⅲ. 결과 = 7 Ⅳ. 고찰 = 12 Ⅴ. 결론 = 16 Reference = 18 Abstract = 2

이산화티타늄 나노튜브 어레이에 로딩된 이산화루테늄 전극의 전기화학적 기체발생 촉매특성

학위논문 (석사)-- 서울대학교 대학원 : 공과대학 재료공학부, 2018. 8. 김진영.Ruthenium dioxide (RuO2) has an advantage of various chemical reactions like dehydrogenation, gas phase oxidation of HCl, and chloro-alkali process. In order to enhance stability of RuO2-based catalysts, the use of TiO2 is successful in recent years. In general, nanostructured scaffolds with the large relative surface area are adopted in the catalytic reactions for maximizing the number of active sites. For the electrocatalytic reactions, however, the scaffold should be conducting enough so that the charges required for the redox reaction can be transported to the surface of the loaded RuO2 catalysis. In the same context, TiO2 nanotube arrays (NTAs) can be a promising scaffold for the CER reaction, because it can transport charges (as evidenced in the solar cell or PEC applications) and it can be a good combination with RuO2 (as evidenced by DSA®). In addition, the nanoscale morphologies (e.g. tube length, pore diameter, and wall thickness), crystalline structure (e.g. crystalline phase and preferred orientation), and the electrical properties (e.g. conductivity) can be precisely controlled by the processing parameters. In this study, we firstly report the RuO2-loaded TiO2 NTAs as an efficient nanostructure electrode for the electrocatalytic CER process. Nanostructruring is well-known for enhancing the catalysts activity, we design TiO2 based nanostructure to investigate more active catalysts. The samples have been prepared electrochemically (i.e. electrochemical anodization for preparing TiO2 NTAs and electrochemical deposition for loading RuO2) and the dependence of the CER performance on the materials properties of the composite electrodes such as the crystallinity and electrical conductivity have been investigated. It has been found that the conductivity of the electrode under the anodic polarization is essential for achieving good CER performance, and the black TiO2 prepared by annealing as-anodized NTAs under an Ar atmosphere has been found to be the best scaffold for the RuO2 catalysis.1. Introduction 1 1.1 Chlorine Evolution Reaction (CER) 1 1.1.1 Chlor alkali process 1 1.1.2 Mechanism of chlorine evolution reaction 8 1.1.3 Recent research trend and literature review 12 1.2 TiO2 nanotube arrays (TiO2 NTAs) 22 1.2.1 Brief outline of TiO2 22 1.2.2 Self organized TiO2 Nanotube arrays 25 1.2.2.1 Factors affecting the morphology of TiO2 NTAs 29 1.2.3 Mechanistic regime 35 1.2.4 Black TiO2 and modification of physical properties of TiO2 NTAs 37 2. Experimental Details 44 2.1. Preparation of TiO2 nanotube arrays (TiO2 NTAs) 44 2.2. Preparation of the RuO2 NTAs electrode 45 2.3. Materials Characterization 46 2.4. Electrochemical measurements 47 3. Results and discussion 55 3.1 Preparation of TiO2 NTAs 55 3.1.1 voltage dependence of TiO2 NTAs 55 3.1.2 effect of pore widening 60 3.2 Preparation of TiO2@RuO2 electrodes 62 3.2.1 pulse electrodeposition and constant current electrodeposition 62 3.2.2 effect of annealing condition 71 3.3 Characterization of TiO2@RuO2 electrodes 73 3.3.1 Materials characterization 73 3.3.2 Electrochemical analysis 79 3.3.2.1 Evaluation of catalytic activity 79 3.3.2.2 Evaluation of conductivity under different bias 89 4. Conclusions 95 References 96 Abstract in Korean 115Maste