Department of Internal Medicine, National Taiwan University Hospital, Taiwan.
Pharmacogenet Genomics. 2011 Dec;21(12):829-36. doi: 10.1097/FPC.0b013e32834bfff1.
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.
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.
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.
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.
本研究旨在分析噻唑烷二酮（TZD）相关水肿与遗传和临床变量的关系，并建立一个简单的评分系统来预测发生 TZD 相关水肿的风险。
在 268 名接受 TZD 治疗 2 型糖尿病的患者中，有 58 名（21.6%）发生了外周水肿。对涉及钠和水重吸收的候选基因的 28 个标签单核苷酸多态性（SNP）进行了基因分型。使用 Cox 回归和 logistic 回归模型分析不同基因型和加权基因型评分与 TZD 相关水肿风险的相关性。
发生水肿的患者年龄较大，主要为女性，体重增加较多。AQP2 rs296766 T 等位基因与 TZD 相关水肿相关[等位基因 P=0.0059；比值比（OR），2.89；95%置信区间（CI），1.61-5.17]。SLC12A rs12904216 G 等位基因具有边缘显著性（等位基因 P=0.049），但在经过多重检验校正后消失。在基于两个 SNP（AQP2 rs296766 和 SLC12A1 rs12904216）的患者中，加权基因型评分处于前四分之一的患者发生 TZD 相关水肿的风险更高（OR，16.45；95%CI，3.05-88.76）。将两个 SNP 的加权遗传评分或所有 SNP 与年龄和性别信息相结合，显著提高了对 TZD 相关水肿的预测能力。我们还开发了一个简单的基于危险因素的评分系统来预测个体发生 TZD 相关水肿的风险。
包括 AQP2 rs296766 和/或 SLC12A rs12904216 SNP 的年龄、性别和遗传信息在内的临床适用预测模型可以用来估计 2 型糖尿病患者发生 TZD 相关水肿的风险。
