title: Genetic predisposition and nongenetic risk factors of thiazolidinedione-related edema in patients with type 2 diabetes.
abstract: OBJECTIVE
  This study aimed to analyze the association of thiazolidinedione (TZD)-related edema with genetic and clinical variables and develop a simple points system to predict the risk of developing TZD-related edema.
  
  
  METHODS
  Fifty-eight (21.6%) of 268 individuals who received TZD for type 2 diabetes developed peripheral edema. Twenty-eight tag single nucleotide polymorphisms (SNPs) from candidate genes involved in sodium and water reabsorption were genotyped. Cox regression and logistic regression models were used to analyze the associations of different genotypes and weighted genotypic scores with TZD-related edema risk.
  
  
  RESULTS
  Individuals with edema were older, predominantly female, and had greater weight gain. The AQP2 rs296766 T allele was associated with TZD-related edema [allelic P=0.0059; odds ratio (OR), 2.89; 95% confidence interval (CI), 1.61-5.17]. The SLC12A rs12904216 G allele had borderline significance (allelic P=0.049), which disappeared after correction for multiple testing. Patients with two SNP-based (AQP2 rs296766 and SLC12A1 rs12904216), who weighted genotypic scores within the top quartile, had a higher risk of developing TZD-related edema (OR, 16.45; 95% CI, 3.05-88.76). Combining the weighted genetic scores of two SNPs or all SNPs with age and sex information significantly improved the predictive power for TZD-related edema. We also developed a simple risk factor-based points system to predict an individual's risk of developing TZD-related edema.
  
  
  CONCLUSIONS
  A clinically applicable prediction model including age, sex, and genetic information from AQP2 rs296766 and/or SLC12A rs12904216 SNPs can be developed to estimate the risk of TZD-related edema in type 2 diabetes patients.
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, Taiwan.
authors.forename: Tien-Jyun
authors.initials: TJ
authors.lastname: Chang
authors.forename: Pi-Hua
authors.initials: PH
authors.lastname: Liu
authors.forename: Yi-Chi
authors.initials: YC
authors.lastname: Liang
authors.forename: Yi-Cheng
authors.initials: YC
authors.lastname: Chang
authors.forename: Yi-Der
authors.initials: YD
authors.lastname: Jiang
authors.forename: Hung-Yuan
authors.initials: HY
authors.lastname: Li
authors.forename: Min-Tzu
authors.initials: MT
authors.lastname: Lo
authors.forename: Harn-Shen
authors.initials: HS
authors.lastname: Chen
authors.forename: Lee-Ming
authors.initials: LM
authors.lastname: Chuang
mesh_terms: D000368:Aged; D000483:Alleles; D051399:Aquaporin 2 / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000235:genetics; D004487:Edema / Q000139:chemically induced* / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D028021:Sodium-Potassium-Chloride Symporters / Q000235:genetics; D064466:Solute Carrier Family 12, Member 1; D045162:Thiazolidinediones / Q000009:adverse effects*
chemical_list: C496023:AQP2 protein, human; D051399:Aquaporin 2; D007004:Hypoglycemic Agents; C578714:SLC12A1 protein, human; D028021:Sodium-Potassium-Chloride Symporters; D064466:Solute Carrier Family 12, Member 1; D045162:Thiazolidinediones; C089946:2,4-thiazolidinedione