AbstractAims  Peroxisome proliferator‐activated receptor γ co‐activator 1β (PPARGC1B) may play an important role in obesity and Type 2 diabetes mellitus (T2DM). In an effort to identify genetic polymorphisms in potential candidate genes for T2DM, genetic associations of PPARGC1B were examined in a Korean T2DM study.Methods  We have sequenced the PPARGC1B, and examined its association with T2DM and diabetic phenotypes in a Korean T2DM study (775 T2DM patients and 316 control subjects) using the TaqMan method. Logistic and multiple regression models were employed to analyse the genetic contributions of polymorphisms. Nineteen polymorphisms were identified in PPARGC1B.Results  By logistic regression analysis controlling for age and sex as covariates, one non‐synonymous single‐nucleotide polymorphism (SNP; +102605C>A; Arg292Ser) in exon 5 showed marginal significant associations with the risk of T2DM. The allele frequency of the minor allele [‘A (= Ser)’ allele of +102605C>A] was lower among T2DM patients (frequency = 0.101) than among control subjects (frequency = 0.135) [P = 0.03, OR = 0.71 (95% CI: 0.51–0.94)]. Furthermore, serum triglyceride level was also associated with this non‐synonymous SNP (+102605C>A; Arg292Ser) in exon 5 among controls (P = 0.03 in the dominant analysing model). Serum triglyceride levels [1.46 ± 0.70 (log‐transformed value; 0.12 ± 0.18)] were lower in individuals who carry one or two copies of minor alleles than among others [1.60 ± 0.85 (log‐transformed value; 0.16 ± 0.21)].Conclusion  The present study provides, for the first time, information about genetic polymorphisms in PPARGC1B and putative associations of one non‐synonymous SNP with the risk of T2DM and serum triglyceride (TG) levels in the Korean population, although this result was not significant after correction for multiple testing.