OBJECTIVE To elucidate the influence of fetal genotype in both non-diabetic gravidas and pregnant women on gestational diabetes mellitus (GDM) through analysis of the genotype discrepancy between maternal and fetal Pro12Ala single nucleotide polymorphism (SNP) of peroxisome proliferator-activated receptor gamma 2 (PPARG2) genes. METHODS Pregnant women, who delivered in the Obstetrics and Gynecology Hospital of Fudan University from October 2005 to February 2007, and their newborn babies were selected, and were divided into GDM and control group. The GDM group consisted of 55 gravidas with GDM and 40 newborns born to the GDM mothers, and the control group consisted of 173 healthy gravidas and their 50 neonates. Polymerase chain reaction-denaturing high-performance liquid chromatography was applied to detect the distribution of PPARG2 Pro12Ala alleles in all subjects. The concentrations of plasma fasting blood sugar (FBS) and several bio-markers of lipids, including total cholesterol, triglyceride, apoprotein A, high-density lipoprotein and low-density lipoprotein, were also tested for the mothers. RESULTS (1) No significant difference was found in the frequencies of Pro/Pro genotype between the GDM mothers and control mothers (94.6% vs 90.8%, P > 0.05), nor between the GDM offspring and control offspring (95.0% vs 94.0%, P > 0.05) or between the GDM mothers and GDM offspring (P > 0.05). The same was shown in the frequencies of Pro/Ala genotype both between the GDM mothers and control mothers (5.5% vs 9.2%, P > 0.05) and between the GDM offspring and control offspring (2.5% vs 3.0%, P > 0.05). (2) Within both GDM and control group, the maternal FBS and various lipids concentrations of Pro/Pro genotype gravidas showed no significant difference compared to those of Pro/Ala genotype mothers (P > 0.05). (3) Based on the four possible PPARG2 genotype pairs between the mothers and fetuses, Pro/Pro mother and her Pro/Pro fetus, Pro/Ala mother and her Pro/Ala fetus, Pro/Ala mother and her Pro/Pro fetus, and Pro/Pro mother and her Pro/Ala fetus, less Pro/Pro pairs and more Pro/Ala pairs were found in the GDM group than in the control (72.5% vs 92.0%, P = 0.014; 27.5% vs 6.0%, P < 0.05). CONCLUSIONS Neither the maternal nor the offspring's Pro/Ala genotypes is associated with the genesis of GDM. However, the discrepancy of PPARG2 Pro12Ala polymorphism between mother and her fetus implies a possible cause of GDM.