Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China.
Department of Pharmacy, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
BMC Med Genomics. 2021 Nov 12;14(1):267. doi: 10.1186/s12920-021-01108-5.
Genetic polymorphisms in the PPARD and NOS1AP is associated with type 2 diabetes mellitus (T2DM); however, there is no evidence about its impact on the therapeutic efficacy of nateglinide. This study was designed to investigate a potential association of PPARD rs2016520 (T/C) and NOS1AP rs12742393 (A/C) polymorphisms with efficacy of nateglinide in newly diagnosed Chinese patients with type 2 diabetes mellitus (T2DM).
Sixty patients with newly diagnosed T2DM were enrolled to identify PPARD rs2016520 and NOS1AP rs12742393 genotypes using the polymerase chain reaction-restriction fragment length polymorphism assay (PCR-RFLP). All subjects were treated with nateglinide (360 mg/day) for 8 weeks. Anthropometric measurements, clinical laboratory tests were obtained at baseline and after 8 weeks of nateglinide treatment.
After nateglinide treatment for 8 consecutive weeks, patients with at least one C allele of PPARD rs2016520 showed a smaller decrease in post plasma glucose (PPG), homeostasis model assessment for beta cell function (HOMA-B) than those with the TT genotype did (P < 0.05). In patients with the AA genotype of NOS1AP rs12742393, the drug showed better efficacy with respect to levels of fasting plasma glucose (FPG), fasting serum insulin (FINS), HOMA-B and homeostasis model assessment for insulin resistance (HOMA-IR) than in patients with the AC + CC genotype (P < 0.05). NOS1AP rs12742393 genotype distribution and allele frequency were associated with responsiveness of nateglinide treatment (P < 0.05).
The PPARD rs2016520 and NOS1AP rs12742393 polymorphisms were associated with nateglinide monotherapy efficacy in Chinese patients with newly diagnosed T2DM.
Chinese Clinical Trial Register ChiCTR13003536, date of registration: May 14, 2013.
过氧化物酶体增殖物激活受体 δ（PPARD）和一氧化氮合酶 1 蛋白（NOS1AP）基因多态性与 2 型糖尿病（T2DM）有关；然而，尚无证据表明其对那格列奈治疗效果有影响。本研究旨在探讨 PPARD rs2016520（T/C）和 NOS1AP rs12742393（A/C）多态性与新诊断为 2 型糖尿病（T2DM）的中国患者那格列奈疗效之间的潜在关联。
纳入 60 例新诊断为 T2DM 的患者，使用聚合酶链反应-限制性片段长度多态性分析（PCR-RFLP）鉴定 PPARD rs2016520 和 NOS1AP rs12742393 基因型。所有患者均接受那格列奈（360mg/天）治疗 8 周。在基线和那格列奈治疗 8 周后，进行人体测量学测量和临床实验室检查。
连续 8 周那格列奈治疗后，PPARD rs2016520 至少有一个 C 等位基因的患者与 TT 基因型患者相比，餐后血糖（PPG）和胰岛β细胞功能的稳态模型评估（HOMA-B）下降幅度较小（P<0.05）。NOS1AP rs12742393 为 AA 基因型的患者，与 AC+CC 基因型患者相比，空腹血糖（FPG）、空腹血清胰岛素（FINS）、HOMA-B 和胰岛素抵抗的稳态模型评估（HOMA-IR）水平的药物疗效更好（P<0.05）。NOS1AP rs12742393 基因型分布和等位基因频率与那格列奈治疗的反应性相关（P<0.05）。
PPARD rs2016520 和 NOS1AP rs12742393 多态性与新诊断为 T2DM 的中国患者那格列奈单药治疗疗效相关。
中国临床试验注册中心 ChiCTR13003536，注册日期：2013 年 5 月 14 日。
