Genomic Variant in IL-37 Confers A Significant Risk of Coronary Artery Disease.
The interleukin 1 family plays an important role in the immune and inflammatory responses. Coronary artery disease (CAD) is a chronic inflammatory disease. However, the genetic association between IL-37, the seventh member of the IL-1 family, and CAD is unknown. Here we show that a single nucleotide polymorphism in the IL-37 gene (rs3811047) confers a significant risk of CAD. We have performed an association analysis between rs3811047 and CAD in two independent populations with 2,501 patients and 3,116 controls from China. Quantitative RT-PCR analysis has been performed to determine if the IL-37 expression level is influenced by rs3811047. We show that the minor allele A of rs3811047 is significantly associated with CAD in two independent populations under a recessive model (Padj= 5.51 × 10-3/OR = 1.56 in the GeneID Northernern population and Padj= 1.23 × 10-3/OR = 1.45 in the GeneID Central population). The association became more significant in the combined population (Padj= 9.70 × 10-6/OR = 1.47). Moreover, the association remains significant in a CAD case control population matched for age and sex. Allele A of rs3811047 shows significant association with a decreased mRNA expression level of IL-37 (n = 168, P = 3.78 × 10-4). These data suggest that IL37 is a new susceptibility gene for CAD, which provides a potential target for the prevention and treatment of CAD.
Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Cardio-X Institute, Huazhong University of Science and Technology, Wuhan, P. R. China.|BGI-Wuhan, Wuhan 430075, China; BGI-Shenzhen, Shenzhen 518083, China.
Dan
D
Yin
Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Cardio-X Institute, Huazhong University of Science and Technology, Wuhan, P. R. China.
Duraid Hamied
DH
Naji
Cardiovascualr Hospital, the First Affiliated Hospital of Dalian Medical University, Dalian, Wuhan, P. R. China.
Yunlong
Y
Xia
Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Cardio-X Institute, Huazhong University of Science and Technology, Wuhan, P. R. China.
Sisi
S
Li
Center of Prenatal Diagnosis, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Hunan, P. R. China.
Ying
Y
Bai
Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Cardio-X Institute, Huazhong University of Science and Technology, Wuhan, P. R. China.
Guiqing
G
Jiang
Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Cardio-X Institute, Huazhong University of Science and Technology, Wuhan, P. R. China.
Yuanyuan
Y
Zhao
Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Cardio-X Institute, Huazhong University of Science and Technology, Wuhan, P. R. China.
Xiaojing
X
Wang
Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Cardio-X Institute, Huazhong University of Science and Technology, Wuhan, P. R. China.
Yufeng
Y
Huang
Key Laboratory for Molecular Diagnosis of Hubei Province, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, P. R. China.
Shanshan
S
Chen
Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Cardio-X Institute, Huazhong University of Science and Technology, Wuhan, P. R. China.
Jingjing
J
Fa
Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Cardio-X Institute, Huazhong University of Science and Technology, Wuhan, P. R. China.
Chengcheng
C
Tan
Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Cardio-X Institute, Huazhong University of Science and Technology, Wuhan, P. R. China.
Mengchen
M
Zhou
Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Cardio-X Institute, Huazhong University of Science and Technology, Wuhan, P. R. China.
Yingchao
Y
Zhou
Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Cardio-X Institute, Huazhong University of Science and Technology, Wuhan, P. R. China.
Longfei
L
Wang
Cardiovascualr Hospital, the First Affiliated Hospital of Dalian Medical University, Dalian, Wuhan, P. R. China.
Ying
Y
Liu
Cardiovascualr Hospital, the First Affiliated Hospital of Dalian Medical University, Dalian, Wuhan, P. R. China.
Feifei
F
Chen
Cardiovascualr Hospital, the First Affiliated Hospital of Dalian Medical University, Dalian, Wuhan, P. R. China.
Jingqiu
J
Liu
Center for Cardiovascular Genetics, Department of Molecular Cardiology, Lerner Research Institute, Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio, USA.|Department of Molecular Medicine, Department of Genetics and Genome Science, Case Western Reserve University, Cleveland, OH, USA.
Qiuyun
Q
Chen
Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Cardio-X Institute, Huazhong University of Science and Technology, Wuhan, P. R. China.
Xin
X
Tu
Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Cardio-X Institute, Huazhong University of Science and Technology, Wuhan, P. R. China.
Chengqi
C
Xu
Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Cardio-X Institute, Huazhong University of Science and Technology, Wuhan, P. R. China.|Center for Cardiovascular Genetics, Department of Molecular Cardiology, Lerner Research Institute, Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio, USA.|Department of Molecular Medicine, Department of Genetics and Genome Science, Case Western Reserve University, Cleveland, OH, USA.
Qing K
QK
Wang
D000368:Aged; D000483:Alleles; D002681:China; D003324:Coronary Artery Disease / Q000235:genetics* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
C508587:IL37 protein, human; D007375:Interleukin-1