Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011881 (diabetic nephropathy)
 10,836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This review considers the 250+ papers concerning the association of the angiotensin converting enzyme (ACE) gene insertion/deletion polymorphism (rs1799752) and various disease conditions published in 2009. The deletion allele occurs in approximately 55% of the population and is associated with increased activity of the ACE enzyme. It might be predicted that the D allele, therefore, might be associated with pathologies involving increased activity of the renin-angiotensin system. The D allele was seen to be associated with an increased risk of hypertension, pre-eclampsia, heart failure, cerebral infarct, diabetic nephropathy, encephalopathy, asthma, severe hypoglycaemia in diabetes, gastric cancer (in Caucasians) and poor prognosis following kidney transplant. On the positive side, the D allele appears to offer protection against schizophrenia and chronic periodontitis and confers greater up-per-body strength in old age. The I allele, meanwhile, offers improved endurance/athletic performance and aerobic capacity as determined by lung function tests, although it does increase the risk of oral squamous cell carcinoma and obstructive sleep apnoea in hypertensives.
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PMID:Implications of the angiotensin converting enzyme gene insertion/deletion polymorphism in health and disease: a snapshot review. 2153 87

In most complex diseases, much of the heritability remains unaccounted for by common variants. It has been postulated that lower-frequency variants contribute to the remaining heritability. Here, we describe a method to test for polygenic inheritance from lower-frequency variants by using GWAS summary association statistics. We explored scenarios with many causal low-frequency variants and showed that there is more power to detect risk variants than to detect protective variants, resulting in an increase in the ratio of detected risk to protective variants (R/P ratio). Such an excess can also occur if risk variants are present and kept at lower frequencies because of negative selection. The R/P ratio can be falsely elevated because of reasons unrelated to polygenic inheritance, such as uneven sample sizes or asymmetric population stratification, so precautions to correct for these confounders are essential. We tested our method on published GWAS results and observed a strong signal in some diseases (schizophrenia and type 2 diabetes) but not others. We also explored the shared genetic component in overlapping phenotypes related to inflammatory bowel disease (Crohn disease [CD] and ulcerative colitis [UC]) and diabetic nephropathy (macroalbuminuria and end-stage renal disease [ESRD]). Although the signal was still present when both CD and UC were jointly analyzed, the signal was lost when macroalbuminuria and ESRD were jointly analyzed, suggesting that these phenotypes should best be studied separately. Thus, our method may also help guide the design of future genetic studies of various traits and diseases.
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PMID:An excess of risk-increasing low-frequency variants can be a signal of polygenic inheritance in complex diseases. 2460 88

Small non-coding RNAs including microRNAs (miRNAs) have been recently recognized as important regulators of gene expression. MicroRNAs play myriads of roles in physiological processes as well as in the pathogenesis of a number of diseases by translational repression or mRNA destabilization of numerous target genes. The miR-106b-25 cluster is highly conserved in vertebrates and consists of three members including miR-106b, miR-93 and miR-25. MiR-106b and miR-93 share the same seed sequences; however, miR-25 has only a similar seed sequence resulting in different predicted target mRNAs. In this review, we specifically focus on the role of miR-25 in healthy and diseased conditions. Many of miR-25 target mRNAs are involved in biological processes such as cell proliferation, differentiation, and migration, apoptosis, oxidative stress, inflammation, calcium handling, etc. Therefore, it is no surprise that miR-25 has been reported as a key regulator of common cancerous and non-cancerous diseases. MiR-25 plays an important role in the pathogenesis of acute myocardial infarction, left ventricular hypertrophy, heart failure, diabetes mellitus, diabetic nephropathy, tubulointerstitial nephropathy, asthma bronchiale, cerebral ischemia/reperfusion injury, neurodegenerative diseases, schizophrenia, multiple sclerosis, etc. MiR-25 is also a well-described oncogenic miRNA playing a crucial role in the development of many tumor types including brain tumors, lung, breast, ovarian, prostate, thyroid, oesophageal, gastric, colorectal, hepatocellular cancers, etc. In this review, our aim is to discuss the translational therapeutic role of miR-25 in common diseased conditions based on relevant basic research and clinical studies.
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PMID:A myriad of roles of miR-25 in health and disease. 2976 62