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The implications of relationships between human diseases and metabolic subpathways.

ABSTRACT: One of the challenging problems in the etiology of diseases is to explore the relationships between initiation and progression of diseases and abnormalities in local regions of metabolic pathways. To gain insight into such relationships, we applied the "k-clique" subpathway identification method to all disease-related gene sets. For each disease, the disease risk regions of metabolic pathways were then identified and considered as subpathways associated with the disease. We finally built a disease-metabolic subpathway network (DMSPN). Through analyses based on network biology, we found that a few subpathways, such as that of cytochrome P450, were highly connected with many diseases, and most belonged to fundamental metabolisms, suggesting that abnormalities of fundamental metabolic processes tend to cause more types of diseases. According to the categories of diseases and subpathways, we tested the clustering phenomenon of diseases and metabolic subpathways in the DMSPN. The results showed that both disease nodes and subpathway nodes displayed slight clustering phenomenon. We also tested correlations between network topology and genes within disease-related metabolic subpathways, and found that within a disease-related subpathway in the DMSPN, the ratio of disease genes and the ratio of tissue-specific genes significantly increased as the number of diseases caused by the subpathway increased. Surprisingly, the ratio of essential genes significantly decreased and the ratio of housekeeping genes remained relatively unchanged. Furthermore, the coexpression levels between disease genes and other types of genes were calculated for each subpathway in the DMSPN. The results indicated that those genes intensely influenced by disease genes, including essential genes and tissue-specific genes, might be significantly associated with the disease diversity of subpathways, suggesting that different kinds of genes within a disease-related subpathway may play significantly differential roles on the diversity of diseases caused by the corresponding subpathway.

SUBMITTER: Li X

PROVIDER: S-EPMC3117879 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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The implications of relationships between human diseases and metabolic subpathways.

Li Xia X Li Chunquan C Shang Desi D Li Jing J Han Junwei J Miao Yingbo Y Wang Yan Y Wang Qianghu Q Li Wei W Wu Chao C Zhang Yunpeng Y Li Xiang X Yao Qianlan Q

PloS one 20110617 6

One of the challenging problems in the etiology of diseases is to explore the relationships between initiation and progression of diseases and abnormalities in local regions of metabolic pathways. To gain insight into such relationships, we applied the "k-clique" subpathway identification method to all disease-related gene sets. For each disease, the disease risk regions of metabolic pathways were then identified and considered as subpathways associated with the disease. We finally built a disea ...[more]

PMID: 21695054

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Project description:Carotenoids have potential antioxidant and anti-inflammatory effects; their protective roles are of particular interest in the pathogenesis of metabolic syndrome (MetS). The reflection spectroscopy method has been recently developed to noninvasively measure skin carotenoid (SC) levels, which highly correlates with serum concentration of carotenoids. The relationship between SC levels and metabolic syndrome has been investigated. We aimed to identify the differences in patient characteristics and SC levels between participants with and without MetS in a large health examination population. In addition, the relationships between SC levels and various clinical parameters related to MetS were investigated. SC levels were measured using a reflection spectroscopy. A total of 1812 Japanese participants (859 male, 953 female; mean age ± standard deviation (SD), 57.8 ± 11.0 years) comprised the study population, i.e., participants with MetS (n = 151) and those without MetS (n = 1661). Multivariate logistic regression analysis was performed to identify variables associated with MetS. Compared to controls (377.3 ± 122.8), SC indices were significantly lower in patients with MetS (340.7 ± 112.5, p = 0.0004). Multivariate models also suggested that lower SC was significantly associated with MetS after adjustment for age, sex, smoking habit, and other potential risk factors for MetS. Furthermore, male gender (p < 0.0001), smoking habit (p < 0.0001) and worse lipid profiles (i.e., serum triglyceride (r = -0.1039, p < 0.0001), high-density lipoprotein (r = 0.1259, p < 0.0001), and usage of hypolipidemic agents (p = 0.0340)) were significantly associated with lower SC levels. The current study indicated that lower SC levels were significantly associated with MetS. This study highlights the antioxidant capacity of carotenoids in patients with MetS and the clinical utility of non-invasive and cost-effective SC measurement to detect participants who are at risk of developing MetS in a large population.

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The implications of relationships between human diseases and metabolic subpathways.

Publications

The implications of relationships between human diseases and metabolic subpathways.

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