한국인에서의 MACROD2 유전자 다형성과 고혈압 상관성 연구
MACROD2 Polymorphisms Are Associated with Hypertension in Korean Population
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초록
고혈압은 유전적, 환경적 요인들이 복합적으로 작용하여 발생하는 질환으로, 선진국들의 경우에는 성인들의 30% 이상이고혈압 상태인 매우 유병률이 높은 만성 질환이다. 고혈압에 영향을 미치는 유전적 요인들 중에서 MACROD2 유전자의 변이들이 백인 중심의 코호트 연구에서 혈압 및 고혈압 상태와 상관관계가 있다는 보고들이 있다. 이에 본 연구에서는 질병관리본부에서 생산 구축한 한국인 유전체 역학 자료를 바탕으로 MACROD2 유전자 영역의 유전 변이들을 선택 추출한 후에 고혈압 상태에 대한 로지스틱 회귀분석을 시행하였고, 수축기 혈압과 이완기 혈압에 대해서는 선형 회기 분석을 진행하였다. 그결과 고혈압 상태에서 16개 SNP들이 유의한 상관관계를 보여주었고, 이들 중 2개의 SNP (rs16996211, rs6034240)은 혈압에서도 통계적 유의성을 보여주고 있다. 가장 유의성이 높은rs16996211은 고혈압의 상대적 위험도가 0.85 (CI: 0.76∼ 0.95, P=3.1×10‒3)이고, 수축기 혈압은 (beta=‒0.75, P=0.024)의 이완기 혈압은(beta=‒0.59, P=0.01)의 상관 분석결과를 보여주었다. 이러한 결과들을 통해 MACROD2 유전자의 다형성은 백인 중심의 서양인 뿐만 아니라 한국인에서도 고혈압과 상관관계가 있는 것을 확인할 있었으며, 이러한 사실은고혈압의 병리 기전에 대한 유전적 상호관계의 이해를 높일 것으로 기대한다.
Abstract
Hypertension is caused by a combination of genetic and environmental factors. In advanced countries, more than 30% of adults have hypertension. Among the genetic factors affecting hypertension, there are reports from European cohort studies that variants of the MACROD2 gene are correlated with blood pressure and the hypertension status. In this study, genetic polymorphisms of the MACROD2 gene region were selected and extracted based on Korean Genome and Epidemiology data, and logistic regression analysis was then performed for the hypertensive state. Linear regression analysis was also performed for the systolic and diastolic blood pressure. As a result, 16 SNPs showed a statistically significant association with a hypertensive state, and 2 SNPs (rs16996211, rs6034240) showed statistical significance, even in blood pressure. The most significant rs16996211 had a relative risk of hypertension of 0.85 (CI: 0.76∼0.95, P=3.1×10‒3), as well as an association with the systolic blood pressure (beta=‒0.75, P=0.024) and diastolic blood pressure (beta=‒0.59, P=0.01). These results suggest that polymorphisms of the MACROD2 gene are associated with hypertension in both Caucasians and Koreans, and highlight the potential genetic correlations with the pathogenesis of hypertension.
참고문헌 (25)
- Carretero OA, "Essential hypertension. Part I: definition and etiology", Circulation, 101, pp.329~335 (2000)
- Larry E. Fields, "The Burden of Adult Hypertension in the United States 1999 to 2000", Hypertension, 44(4), pp.398~404 (2004), Ovid Technologies (Wolters Kluwer Health)[DOI]
- Lawes CM, "Global burden of blood-pressure-related disease, 2001", Lancet, 371, pp.1513~1518 (2008)[DOI]
- Yannoutsos A, "Optimal blood pressure target in stroke prevention", Curr Opin Neurol, 30, pp.8~14 (2017)[DOI]
- 진현석, "Replication of an African-American GWAS on blood pressure and hypertension in the Korean population", Genes & Genomics, 33(2), pp.127~132 (2011), 한국유전학회
- "The 7th Korea National Health and Nutrition Examination Survey (KNHANES VII-1)" (2018)[URL]
- L. Yang, "Association of SNPs in the PPARγ gene and hypertension in a Mongolian population", Genetics and Molecular Research, 14(4), pp.19295~19308 (2015), Genetics and Molecular Research[DOI]
- Weixing Li, "The -344C", T polymorphism in the CYP11B2 gene is associated with essential hypertension in the Chinese, 2014, pp.15(2), 150~155[DOI]
- Li Qin, "Associations SELE Gene Haplotype Variant and Hypertension in Mongolian and Han Populations", Internal Medicine, 54(3), pp.287~293 (2015), Japanese Society of Internal Medicine[DOI]
- Slavin TP, "Two-marker association tests yield new disease associations for coronary artery disease and hypertension", Hum Genet, 130, pp.725~733 (2011)[DOI]
- Yi-Cheng Chang, "Genome-wide scan for circulating vascular adhesion protein-1 levels: MACROD2 as a potential transcriptional regulator of adipogenesis", Journal of Diabetes Investigation, 9(5), pp.1067~1074 (2018), Wiley[DOI]
- Kelly TN, "Genome-wide association study meta-analysis reveals transethnic replication of mean arterial and pulse pressure loci", Hypertension, 62, pp.853~859 (2013)[DOI]
- Zhu X, "Detecting rare variants for complex traits using family and unrelated data", Genet Epidemiol, 34, pp.171~187 (2010)[DOI]
- Maas NM, "The C20orf133 gene is disrupted in a patient with Kabuki syndrome", J Med Genet, 44, pp.562~569 (2007)[DOI]
- Pettersson M, "Copy number variants are enriched in individuals with early-onset obesity and highlight novel pathogenic pathways", J Clin Endocrinol Metab, 102, pp.3029~3039 (2017)[DOI]
- Cho YS, "A large-scale genome-wide association study of Asian populations uncovers genetic factors influencing eight quantitative traits", Nat Genet, 41, pp.527~534 (2009)[DOI]
- Pruim RJ, "Locus zoom : regional visualization of genome-wide association scan results", Bioinformatics, 26, pp.2336~2337 (2010)[DOI]
- Ciullo M, "New susceptibility locus for hypertension on chromosome 8q by efficient pedigree-breaking in an Italian isolate", Hum Mol Genet, 15, pp.1735~1743 (2006)[DOI]
- Cotsapas C, "Common body mass index-associated variants confer risk of extreme obesity", Hum Mol Genet, 18, pp.3502~3507 (2009)[DOI]
- Mohseni M, "MACROD2 over expression mediates estrogen independent growth and tamoxifen resistance in breast cancers", Proc Natl Acad Sci U S A, 111, pp.17606~17611 (2014)[DOI]
- Sakthianandeswaren A, "MACROD2 haploinsufficiency impairs catalytic activity of PARP1 and promotes chromosome instability and growth of intestinal tumors", Cancer Discov, 8, pp.988~1005 (2018)[DOI]
- Jin HS, "Age-dependent association of the polymorphisms in the mitochondria-shaping gene, OPA1, with blood pressure and hypertension in Korean population", Am J Hypertens, 24, pp.1127~1135 (2011)[DOI]
- 진현석, "Gender-specific Association of the ANO1 Genetic Variations with Hypertension", 대한의생명과학회지, 21(3), pp.144~151 (2015), 대한의생명과학회[DOI]
- Hong KW, "Non-synonymous single-nucleotide polymorphisms associated with blood pressure and hypertension", J Hum Hypertens, 24, pp.763~774 (2010)[DOI]
- 김혜경, "CACNA1A Gene Polymorphism is Associated with Hypertension in Korean Population", 대한의생명과학회지, 15(1), pp.31~35 (2009), 대한의생명과학회