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Ah-Ram Park(박아람),Eun-Soon Shin(신은순),Nak-Hoon Son(손낙훈),Yangsoo Jang(장양수),Dong-Jik Shin(신동직) 한국생명과학회 2010 생명과학회지 Vol.20 No.5
혈관 수축력 및 혈압 조절에 관여하는 것으로 알려진 아라키돈산을 물질 대사시키는 CYP2C19 유전자는 최근 심혈관 질환 관련 연구의 새로운 유전자로 제시되고 있다. 본 연구에서는 CYP2C19 유전자의 2 종류 다형성(CYP2C19<SUP>*</SUP>2와 CYP2C19<SUP>*</SUP>3)과 고혈압 간의 연관성을 조사하고자 하였다. 연세대학교 의료원 심장혈관병원에서 수집한 1,241명(환자군: 537명, 대조군: 704명)을 대상으로 SNaPShot™ assay를 이용하여 유전자형을 결정하였다. 두 종류의 다형성 가운데 CYP2C19<SUP>*</SUP>3의 대립인자형 및 유전자형의 빈도 분포가 환자군과 대조군 간에 유의한 차이를 나타냈다(p=0.019, p=0.023). 다중 로지스틱 회귀분석 결과, dominant model에서, CYP2C19<SUP>*</SUP>3 A 대립인자형은 본태성 고혈압과 매우 유의한 연관성을 나타냈다(OR, 0.723, p=0.032). 또한 CYP2C19 G-A haplotype은 고혈압 발생 위험을 매우 유의하게 감소시키는 것으로 조사되었다(OR, 0.714, p=0.015). 따라서 본 연구 결과는 CYP2C19<SUP>*</SUP>3 다형성이 본태성 고혈압 발생에 대한 보호 효과작용에 관여할 것이라는 증거를 제시하고자 한다. In humans, CYP2C19, a member of the cytochrome P450 subfamily, metabolizes arachidonic acid to produce epoxyicosanoid acids, which are involved in vascular tone and regulation of blood pressure (BP). Recent findings suggest that CYP2C19 gene polymorphisms might be considered as a novel candidate gene for cardiovascular disease. We thus focused on the Korean population to explore the association of two polymorphisms (CYP2C19<SUP>*</SUP>2 and <SUP>*</SUP>3) in this gene and essential hypertension (EH). A total of 1,241 participants (537 hypertensive subjects and 704 healthy controls) were recruited from the Yonsei Cardiovascular Genome Center in Korea. The CYP2C19 polymorphisms were genotyped using the SNaPShot™ assay. The allele and genotype frequencies of CYP2C19<SUP>*</SUP>3 showed significant difference between hypertensives and normotensives (P=0.019 and P=0.023, respectively). Logistic regression analysis indicated that the CYP2C19<SUP>*</SUP>3 A allele carriers were significantly associated with EH (OR, 0.723; 95% CI, 0.538-0.972, P=0.032) under a dominant model. In addition, CYP2C19 G-A haplotype (2C19<SUP>*</SUP>2 G-<SUP>*</SUP>3 A combination) was found to significantly reduce EH risk (OR, 0.714, P=0.015). We believe this provides evidence that CYP2C19<SUP>*</SUP>3 polymorphism may contribute to a protective effect in the development of EH.
Leukotriene C4 Synthase 유전자 Promoter 부위 유전적 다형과 아스피린 과민성 천식의 연관성
김상헌 ( Sang Heon Kim ),박흥우 ( Heung Woo Park ),손성욱 ( Seong Wook Sohn ),이상민 ( Sang Min Lee ),오선영 ( Sun Young Oh ),김선신 ( Sun Sin Kim ),박준우 ( Joon Woo Bahn ),장윤석 ( Yoon Seok Chang ),신은순 ( Eun Soon Shin ),이 대한천식알레르기학회 2006 천식 및 알레르기 Vol.26 No.2
Background: The 5-lipoxygenase, 5-lipoxygenase associated protein and leukotriene C4 (LTC4) synthase are enzymes involved in the synthesis of cysteinyl leukotrienes which are known to be important lipid mediators for the development of aspirin-intolerant asthma (AIA). Several studies have evaluated genetic association between polymorphisms of these enzymes and AIA, reporting inconsistent results. Objective: To evaluate the genetic effect of polymorphisms of promoter areas of ALOX5, ALOX5AP and LTC4S genes in the development of AIA. Method: Polymorphisms in promoter areas of ALOX5 (-1761G>A, -1708G>A), ALOX5AP (21A/18A repeat) and LTC4S (-444A>C) were genotyped in patients with AIA (n=44), aspirin-tolerant asthma (ATA, n=104), and healthy-normal controls (NC, n=107). Result: The frequency of LTC4S -444 AC or CC alleles was significantly lower in AIA patients than in ATA patients (19.0% vs. 36.5%, P=0.005, OR=0.23, 95%CI 0.08∼0.64). However, the frequency of these genotypes was not different between AIA and NC (19.0% vs. 24.8%, P=0.458). As to LOX5 -1761G>A, -1708G>A, and ALOX5AP 21A/18A repeat, the frequency of these genotypes was not different between AIA and ATA patients and between AIA and NC. Conclusion: A significant association was found between LTC4S -444A>C and the frequency of AIA. This finding suggests that LTC4 synthase may be involved in the development of AIA in the Korean population. (Korean J Asthma Allergy Clin Immunol 2006;26:115-121)