Methods for diagnosis and treatment of non-insulin dependent diabetes mellitus
A technology for type 2 diabetes and polymorphism, applied in chemical instruments and methods, biochemical equipment and methods, metabolic diseases, etc.
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Embodiment 1
[0152] Establishment of genome-wide microarray experiment database for type 2 diabetes (T2D). A T2D genome-wide functional experiment database was created by collecting and reanalysing all publicly available T2D-related microarray studies (69 experiments, totaling 518 microarrays) at the time of the study. Microarray experiments included multiple tissue types (muscle, liver, fat, and islets) and species (human, mouse, and rat). Each of the 20994 genes in the database was counted and sorted based on the number of microarray experiments in which each gene was significantly dysregulated from 69 microarray study groups.
[0153] All 69 publicly available data from T2D-related genome-wide microarray experiments were collected from three sources (Table 2). First, raw quantitative data of microarrays were selected and downloaded from Gene Expression Omnibus (GEO) by keyword searching for "diabetes" or "diabetics" or "NIDDM" or "non-insulin-dependent". Experiments involving type 1 d...
Embodiment 2
[0180] Example 2 Integration of publicly available microarray experiments found that CD44 is genetically and functionally involved in type 2 diabetes.
[0181] Type 2 diabetes (T2D) is a complex multifactorial disease phenotypically characterized by insulin resistance. Accumulating evidence suggests a causal link between low-grade inflammation (macrophage infiltration) in adipose tissue and the development of insulin resistance / T2D. To find causative T2D-associated genes, we performed a meta-analysis of 518 publicly available T2D-associated microarrays, based on our hypothesis that differentially expressed genes in the T2D crossover model are strong candidates for functional variants. We extracted our best data-driven candidate, the immune receptor CD44, and demonstrated a strong association of the coding variant with T2D in 2830 T2D cases and 1928 controls from two independent cohorts (rs1071695; OR =1.43[1.17-1.74], P=3.9×10 -4 ). We also extracted OPN, a ligand encoding ...
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