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Background  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).    Methods  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.    Results  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).    Conclusions  The  PPARD  rs2016520 and  NOS1AP  rs12742393 polymorphisms were associated with nateglinide monotherapy efficacy in Chinese patients with newly diagnosed T2DM.    Trial registration  Chinese Clinical Trial Register ChiCTR13003536, date of registration: May 14, 2013.

bmc medical genomics

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