Expression-based genome-wide association study links the receptor CD44 in adipose tissue with type 2 diabetes
作者： K. Kodama , M. Horikoshi , K. Toda , S. Yamada , K. Hara
关键词: Type 2 diabetes 、 Gene 、 Inflammation 、 Insulin resistance 、 Genome-wide association study 、 Microarray 、 Endocrinology 、 Diabetes mellitus 、 Internal medicine 、 Immunology 、 Adipose tissue 、 Biology
摘要: Type 2 diabetes (T2D) is a complex, polygenic disease affecting nearly 300 million people worldwide. T2D primarily characterized by insulin resistance, and growing evidence has indicated the causative link between adipose tissue inflammation development of resistance. Genetic association studies have successfully revealed number important genes consistently associated with to date. However, these robust T2D-associated do not fully elucidate mechanisms underlying progression disease. Here, we report an alternative approach, gene expression-based genome-wide study (eGWAS): searching for repeatedly implicated in functional microarray experiments (often publicly available). We performed eGWAS across 130 independent (totally 1,175 case-control microarrays) find additional molecular pathogenesis identified immune-cell receptor CD44 as our top candidate (P = 8.5 × 10−20). found deficiency diabetic mouse model ameliorates resistance also that anti-CD44 antibody treatment decreases blood glucose levels macrophage accumulation high-fat, diet-fed model. Further, humans, observed expressed inflammatory cells obese discovered serum were positively correlated glycemic control. likely plays role rodents humans. Genes available experimental data may unique functionally roles other complex diseases.
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