Correlation between cold and hot pattern in traditional Chinese medicine and gene expression profiles in rheumatoid arthritis

doi:10.1007/s11684-011-0133-y

Front Med

2011, Vol. 5

Issue (2) : 219-228 https://doi.org/10.1007/s11684-011-0133-y

Research Article

Correlation between cold and hot pattern in traditional Chinese medicine and gene expression profiles in rheumatoid arthritis

Miao Jiang¹, Cheng Xiao², Gao Chen^1,3, Cheng Lu¹, Qinglin Zha⁴, Xiaoping Yan⁴, Weiping Kong⁴, Shijie Xu⁵, Dahong Ju⁵, Pu Xu¹, Youwen Zou⁶, Aiping Lu^1,7(

)

1. Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Science, Beijing 100700, China; 2. Sino-Japan Friendship Hospital, Beijing 100029, China; 3. School of Life Sciences, Hubei University, Wuhan 430062, China; 4. National Pharmaceutical Engineering Research Center, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China; 5. Institute of Basic Theory, China Academy of Chinese Medical Science, Beijing 100700, China; 6. University of British Columbia, Vancouver V6T 1Z2, Canada; 7. E-Institute of Shanghai Municipal Education Commission, Shanghai TCM University, Shanghai 200032, China

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Abstract

Clinical manifestations of rheumatoid arthritis (RA) are diversified, and based on the manifestations, the patients with RA could be classified into different patterns under traditional Chinese medicine. These patterns decide the selection of herbal prescription, and thus they can help find a subset of rheumatoid arthritis patients for a type of therapy. In the present study, we combine genome-wide expression analysis with methods of systems biology to identify the functional gene networks for the sets of clinical symptoms that comprise the major information for pattern classification. Clinical manifestations in rheumatoid arthritis were clustered with factor analysis, and two factors (similar to cold and hot patterns in traditional Chinese medicine) were found. Microarray technology was used to reveal gene expression profiles in CD4⁺ T cells from 21 rheumatoid arthritis patients. Protein-protein interaction information for these genes from databases and literature data was searched. The highly-connected regions were detected to infer significant complexes or pathways in this protein-protein interaction network. The significant pathways and function were extracted from these subnetworks using the Biological Network Gene Ontology tool. The genes significantly related to hot and cold patterns were identified by correlations analysis. MAPK signalling pathway, Wnt signaling pathway, and insulin signaling pathway were found to be related to hot pattern. Purine metabolism was related to both hot and cold patterns. Alanine, aspartate, and tyrosine metabolism were related to cold pattern, and histindine metabolism and lysine degradation were related to hot pattern. The results suggest that cold and hot patterns in traditional Chinese medicine were related to different pathways, and the network analysis might be used for identifying the pattern classification in other diseases.

Keywords gene expression profile pathway rheumatoid arthritis traditional Chinese medicine systems biology

Corresponding Author(s): Lu Aiping,Email:lap64067611@126.com

Issue Date: 05 June 2011

Cite this article:

Miao Jiang,Cheng Xiao,Gao Chen, et al. Correlation between cold and hot pattern in traditional Chinese medicine and gene expression profiles in rheumatoid arthritis[J]. Front Med, 2011, 5(2): 219-228.

URL:

https://academic.hep.com.cn/fmd/EN/10.1007/s11684-011-0133-y
https://academic.hep.com.cn/fmd/EN/Y2011/V5/I2/219

Tab.1 Three factors obtained in factor analysis after oblique PROMAX rotation*

Tab.2 TCM cold pattern (factor 1) related genes*

Fig.1 Protein–protein interaction network for TCM cold pattern related genes. The network contains 153 nodes and 1205 edges. Diamonds represent seed nodes, and Circles represent neighbor nodes. All edges represent interactions between the nodes.

Fig.2 The subnetworks made up of highly-connected regions and functions of the nodes in TCM cold pattern related genes. Diamonds represent seed nodes, and circles represent neighbor nodes. All edges represent interactions between the nodes. Clusters with score>2 were considered to be significant (it represents the log of the probability that the network was found by chance). Cluster 1 (A, score=9.15, nodes=20 and edges=183); Cluster 2 (B, score=7.32, nodes=19 and edges=139); Cluster 3 (C, score=6.14, nodes=14 and edges=86); Cluster 4 (D, score=4.46, nodes=11 and edges=49).

Name	ID	Coefficient	P value
Defensin, alpha 4, corticostatin	NM 001925	0.74	0.0006
G protein-coupled receptor	NM 006564	0.71	0.0014
Baculoviral IAP repeat-containing 1	NM 004536	0.67	0.0021
Gamma-glutamyltransferase 2	NM 30474	0.64	0.0003
Leukocyte immunoglobulin-like receptor, subfamily B (with TM and ITIM domains), member 2	NM 005874	0.62	0.0051
Phosphomannomutase 1	NM 002676	0.61	0.0002
Hexokinase 3 (white cell)	NM 002115	0.61	0.0015
Serine/threonine protein kinase MASK	NM 016542	0.59	0.0025
Leukotriene b4 receptor (chemokine receptor-like 1)	NM 000752	0.59	0.0005
Glutamate-ammonia ligase (glutamine synthase)	AL 161952	0.58	0.0017
Beta-1,4 mannosyltransferase	NM 019109	0.58	0.0061
Protection of telomeres 1	NM 015450	0.55	0.0082
KDEL (Lys-Asp-Glu-Leu) endoplasmic reticulum protein retention receptor 2	NM 006854	0.55	0.0087
C-terminal binding protein 2	NM 022802	0.55	0.0140
S100 calcium binding protein A12 (calgranulin C)	NM 005621	0.54	0.0267
Valyl-tRNA synthetase 2	NM 006295	0.54	0.0131
Second mitochondria-derived activator of caspase	AK 001399	0.53	0.0024
A disintegrin and metalloproteinase domain 19 (meltrin beta)	NM 033274	0.53	0.0196
Lactate dehydrogenase A	NM 005566	0.53	0.0020
Homo sapiens cDNA FLJ11458 fis, clone HEMBA1001557	AK 021520	0.52	0.0159
Nuclear autoantigen	NM 014574	0.52	0.0038
Phosphatidylinositol glycan, class K	AF 022913	0.52	0.0047
Gamma-aminobutyric acid (GABA) B receptor, 1	NM 001470	0.51	0.0030
Phospholysine phosphohistidine inorganic pyrophosphate phosphatase	NM 022126	0.51	0.0164
Thymine-DNA glycosylase	NM 003211	0.51	0.0292
H2A histone family, member X	NM 002105	0.51	0.0110
Uridine 5' monophosphate hydrolase 1	NM 016489	0.50	0.0387
Putative methyltransferase	NM 018396	-0.50	0.0126
Eukaryotic translation initiation factor 2C, 2	AF 121255	-0.50	0.0169
N-acylsphingosine amidohydrolase (acid ceramidase)-like	AK 024677	-0.50	0.0089
Enoyl Coenzyme A hydratase 1, peroxisomal	NM 001398	-0.51	0.0150
Killer cell lectin-like receptor subfamily D, member 1	NM 002262	-0.51	0.0071
Isocitrate dehydrogenase 3 (NAD+) beta	NM 006899	-0.53	0.0114
Bromodomain-containing 7	NM 013263	-0.53	0.0069
Apoptosis inhibitor 5	NM 006595	-0.55	0.0008
Eukaryotic translation initiation factor 5	NM 001969	-0.55	0.0066
Erythropoietin	NM 000799	-0.60	0.0056

Tab.3 TCM hot pattern (factor 2) related genes*

Fig.3 Protein–protein interaction network for TCM hot pattern related genes. The network contains 153 nodes and 1205 edges. Diamonds represent seed nodes, and circles represent neighbor nodes. All edges represent interactions between the nodes.

Fig.4 The subnetworks made up of highly-connected regions and functions of the nodes in TCM hot pattern related genes. Diamonds represent seed nodes, and circles represent neighbor nodes. All edges represent interactions between the nodes. Clusters with score>2 were considered to be significant (it represents the log of the probability that the network was found by chance). Cluster 1 (A, score=57.71, nodes=118, and edges=6810); Cluster 2 (B, score=27.42, nodes=66, and edges=1810); Cluster 3 (C, score=14.32, nodes=34 and edges=487); Cluster 4 (D, score=13.14, nodes=35, and edges=460); Cluster 5 (E, score=12.64, nodes=28, and edges=354); Cluster 6 (F, score=7.36, nodes=44, and edges=324); Cluster 7 (G, score=6.04, nodes=23, and edges=139); Cluster 8 (H, score=5.57, nodes=14, and edges=78); Cluster 9 (I, score=5.46, nodes=35, and edges=191); Cluster 10 (J, score=4.18, nodes=16, and edges=67); Cluster 11 (K, score=3.78, nodes=9, and edges=34); Cluster 12 (M, score=2.63, nodes=8, and edges=21); Cluster 13 (N, score=2.5, nodes=40, and edges=100); Cluster 14 (O, score=2.5, nodes=6, and edges=15); Cluster 15 (P, score=2.1, nodes=20, and edges=42).

Tab.4 Different major pathways related to different sets of TCM patterns

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