[논문]한국인에서 NDFIP2 유전적 다형성과 천식의 상관 연구

최은혜; 황다현

doi:10.15324/kjcls.2021.53.3.249

한국인에서 NDFIP2 유전적 다형성과 천식의 상관 연구
Association Study of NDFIP2 Genetic Polymorphism with Asthma in the Korean Population 원문보기

Korean journal of clinical laboratory science : KJCLS = 대한임상검사과학회지, v.53 no.3, 2021년, pp.249 - 256

최은혜 (호서대학교 생명보건대학 임상병리학과) , 황다현 (호서대학교 생명보건대학 임상병리학과)

초록
AI-Helper

천식은 만성 염증성 기도 폐쇄 질환이다. 질병 발생 요인은 다양하며 특히, 유전적 요인과 환경적 요인이 천식 발병에 영향을 미치는 것으로 추정된다. MAPK (mitogen-activated protein kinase)경로는 Th1/Th2의 균형을 조절하며, 천식 발생에 중요한 역할을 하는 것으로 알려져 있다. 본 연구에서는 MAPK 경로를 조절하는 NDFIP2 유전자와 천식 발병과의 상관관계를 분석하였다. 193건의 천식 환자와 3,228건의 정상 대조군의 유전형 데이터를 사용하였다. 그 결과 NDFIP2 안에 있는 4개의 SNP이 천식과 유의한 상관관계와 높은 상대적 위험도를 보였다. 특히 NDFIP2의 rs2783122는 천식과 통계적으로 가장 유의한 연관성을 나타냈다(P-value=9.76×10^-6, OR=1.67, 95% CI=1.33~2.10). NDFIP2 유전자에 대한 SNP imputation 결과 16개의 SNP가 추가 발견되었으며, 모두 유의한 상관 관계와 높은 상대적 위험도를 나타냈다. 유전자형 기반 mRNA 발현 분석을 통해 rs1408049가 minor allele을 가질 경우 유전자 발현이 증가됨을 알 수 있었다. 증가된 NDFIP2 발현은 MAPK 경로를 활성화시켜 천식 발병에 영향을 미칠 수 있다. 결론적으로 NDFIP2의 다형성은 천식 발병과 관련이 있으며, 이는 한국 인구의 천식 관리에 대한 새로운 지침을 제공할 수 있다.

Abstract ▼ AI-Helper

Asthma is a chronic inflammatory airway disease. There are many factors including genetic and environmental factors that influence asthma. The mitogen-activated protein kinase (MAPK) pathway is involved in maintaining the T helper cells 1 and 2 (Th1/Th2) balance and plays an important role in the development of asthma. In this study, the correlation between the NDFIP2 gene that regulates the MAPK pathway and asthma was analyzed. The genetic polymorphism of the NDFIP2 gene was analyzed between 193 asthma patients and 3,228 healthy controls in Korea. As a result, 4 single nucleotide polymorphisms (SNPs) showed a significant correlation (P<0.05) and high relative risk with asthma. Among them, rs2783122 of NDFIP2 showed a statistically significant association with asthma (P-value=9.76×10-6, odds ratio (OR)=1.67, 95% confidence interval (CI)=1.33~2.10). In the SNP imputation on the NDFIP2, 16 SNPs were discovered, and all of them showed significant correlation with asthma and high odds ratio. The genotype-based mRNA expression analysis revealed that the group of minor alleles of rs1408049 showed increased mRNA expression. Increased NDFIP2 expression causes the activation of the MAPK pathway, and this may influence the development of asthma. In conclusion, the polymorphisms of NDFIP2 are associated with asthma development and this can provide the basis for new guidelines for the management of asthma in the Korean population.

주제어

표/그림 (5)

표 Table 1. Asthma cases and controls in the KARE cohort
그림 Figure 1. Regional plot showing SNPs location in NDFIP2. The position of the SNPs in gene are shown at the top. The statistical significance (-log10 P-value) of the association of NDFIP2 with asthma is indicated. The purple diamond (rs2783122) with the most significant SNP number indicates the SNP most strongly associated with asthma. SNPs are shown in the indicated colors according to the levels of linkage disequilibrium (r²). At the bottom, the position (Mb) of the NDFIP2 gene on chromosome 13 (NCBI build 36) is shown along with the gene structures.
표 Table 2. The associated SNPs (P＜0.05) in the NDFIP2 with asthma in the KARE cohort
그림 Figure 2. Genotype-based mRNA expression in tissue using data from the GTEx Portal for SNP (rs1408049) in NDFIP2 (P-value= 0.000066, NES=-0.085). Significant association between genotypes and NDFIP2 expression levels in the GTEx portal was detected with the linear regression model and based on a P-value threshold determined by a web-based eQTL calculator on the GTEx portal. The allele effect on NDFIP2 gene expression levels is shown by boxplots within violin plot. C and G alleles indicate the major and minor allele types, respectively. The white line in the box plot (black) shows the median value of the gene expression at each genotype. When having a minor allele (C>G), it shows that the gene expression level was increased. P-value are calculated with the linear regression model. NES (normalized effect size) means the slope of the linear regression model.
표 Table 3. Result of the regulome DB with SNPs in the NDFIP2

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