title: Genetic disposition and modifiable factors independently associated with anemia in patients with type 2 diabetes mellitus.
abstract: OBJECTIVE
  Anemia is prevalent but under-recognized in patients with diabetes mellitus (DM). Genetic variants in angiotensin-converting enzyme (ACE), tumor necrosis factor-alpha (TNF-α) and erythropoietin (EPO) have been associated with diabetic nephropathy. In the present study, we investigated the associations between anemia and polymorphisms in EPO promoter (rs1617640), TNF-α G-308A and ACE Insertion/Deletion in Chinese patients with type 2 diabetes.
  
  
  METHODS
  Polymorphisms in ACE, TNF-α and EPO were genotyped in 1142 patients. Anemia was defined as hemoglobin (Hb) levels below 12 g/dL for women and 13 g/dL for men.
  
  
  RESULTS
  286 (25%) patients had anemia. Patients with anemia were older, had longer duration of diabetes, worse renal function and more albuminuria. ACE Insertion/Deletion and TNF-a G-308A were not associated with anemia. The frequencies of EPO polymorphism (rs1617640) were significantly different between anemic and nonanemic patients. Patients with TT genotype had higher prevalence of anemia than those with TG and GG. Regression analysis identified EPO SNP, duration of DM, serum albumin, albuminuria and renal function independently associated with anemia. After adjusting for multiple variables, TT and TG genotypes were associated with 3-5-fold increased risk for anemia compared to GG.
  
  
  CONCLUSIONS
  The EPO genotype in Chinese patients with type 2 diabetes is associated with anemia and may help to identify those at risk. Further evaluation of its effect on clinical outcomes in prospective studies may be useful to predict the outcomes of erythropoiesis stimulating therapy, and to individualize anemia management.
authors: Division of Nephrology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang-Gung University College of Medicine, Taoyuan, Taiwan.
authors: Terry Ting-Yu
authors: TT
authors: Chiou
authors: Department of Ophthalmology, Kaohsiung Chang Gung Memorial Hospital and Chang-Gung University College of Medicine, Taoyuan, Taiwan.
authors: Jong-Jer
authors: JJ
authors: Lee
authors: Division of Hematology-Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang-Gung University College of Medicine, Taoyuan, Taiwan.
authors: Ming-Chung
authors: MC
authors: Wang
authors: Division of Metabolism, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang-Gung University College of Medicine, Taoyuan, Taiwan.
authors: Min-Shien
authors: MS
authors: Chung
authors: Department of Laboratory Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang-Gung University College of Medicine, Taoyuan, Taiwan.
authors: Lin-Lin
authors: LL
authors: Pan
authors: Division of Metabolism, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang-Gung University College of Medicine, Taoyuan, Taiwan.
authors: Ching-Jung
authors: CJ
authors: Hsieh
authors: Division of Metabolism, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang-Gung University College of Medicine, Taoyuan, Taiwan.
authors: Siang-Ting
authors: ST
authors: Huang
authors: Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan.
authors: Hsueh-Wen
authors: HW
authors: Chang
authors: Department of Medical Research, Kaohsiung Chang Gung Memorial Hospital and Chang-Gung University College of Medicine, Taoyuan, Taiwan.
authors: Kuender D
authors: KD
authors: Yang
authors: Division of Nephrology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang-Gung University College of Medicine, Taoyuan, Taiwan.
authors: Chien-Te
authors: CT
authors: Lee
authors: Division of Metabolism, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang-Gung University College of Medicine, Taoyuan, Taiwan. Electronic address: ruetsuan@ms2.hinet.net.
authors: Rue-Tsuan
authors: RT
authors: Liu
mesh_terms: D000368:Aged; D000740:Anemia / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D004921:Erythropoietin / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D011446:Prospective Studies; D060888:Real-Time Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000378:metabolism
chemical_list: C554270:EPO protein, human; D014409:Tumor Necrosis Factor-alpha; D004921:Erythropoietin; D004247:DNA; D007703:Peptidyl-Dipeptidase A
keywords: Anemia; EPO gene polymorphism; Type 2 diabetes mellitus