PPARD rs2016520 (T/C) and NOS1AP rs12742393 (A/C) polymorphisms affect therapeutic efficacy of nateglinide in Chinese patients with type 2 diabetes mellitus

• Published in: BMC medical genomics Vol. 14; no. 1; p. 267
• Main Authors: Wang, Tao, Song, Jin-Fang, Zhou, Xue-Yan, Li, Cheng-Lin, Yin, Xiao-Xing, Lu, Qian
• Format: Journal Article
• Language: English
• Published: England BioMed Central 12.11.2021; BMC
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Alleles; Beta cells; China; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - genetics; Enzymes; Female; Gene frequency; Gene polymorphism; Genes; Genetic polymorphism; Genotype; Genotype & phenotype; Glucose; Homeostasis; Humans; Hypoglycemic Agents - therapeutic use; Insulin; Insulin resistance; Male; Metabolic syndrome; Nateglinide; Nateglinide - therapeutic use; NOS1AP; Patients; Peroxisome proliferator-activated receptors; Polymerase chain reaction; Polymorphism; Polymorphism, Single Nucleotide; PPAR delta - genetics; PPARD; Restriction fragment length polymorphism; Treatment Outcome; Type 2 diabetes mellitus; China; Beijing China; Type 2 diabetes mellitus; Genetic polymorphism; NOS1AP; Nateglinide; PPARD
• ISSN: 1755-8794; 1755-8794
• 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.