| BackgroundGestational diabetes mellitus(GDM) is defined as glucose intolerance that occurs or is detected for the first time during pregnancy and may increases the risk for type 2 diabetes mellitus(T2DM) in the later life. GDM is characterized by insulin resistance(IR). The cellular mechanism for the IR of GDM is unknow. Several reports indicate that plasma cell membrane glycoprotein-l(PC-l) K121Q polymorphism may adversely influence insulin sensitivity by inhibiting insulin receptor function and peroxisome proliferators-activated receptor y2 (PPARγ2) P12A polymorphism may also play a role in modulating insulin sensitivity. Both PC-1 K121Q and PPARγ2 P12A polymorphisms may contribute to the pathogenesis of T2DM or obesity. But study on the relationship between the two polymorphisms and GDM is still blank.ObjectiveIt is believed that several genes may act on IR together and there also have interaction among these genes. In this study, we want to investigate the association of PC-1 K121Q and PPARγ2 P12A polymorphisms with GDM and their clinical characteristics in Han nationality women in Tianjin and Hebei province of China. Meanwhile, to assure whether the two genes are susceptible or protective gene to GDM, whether they modulate insulin sensitivity of GDM independently, and whether they interact in determining IR of GDM.Methods100 unrelated subjects were divided into two groups, women with GDM and pregnant women with normal glucose tolerance( n=50 for each group). Cases would be excluded if some conditions occure such as hypertension, hypothyroidism, which may interfere with insulin sensitivity. Two groups were similar in age, parities and gestational weeks. The genotypes of PC-1 K121Q and PPARy2 P12A variants were determined by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) assay in two groups. The clinical data were also analyzed.Results1. The PC-1 121Q allele frequency was higher in women with GDM compared with control group(14% vs. 5%, P<0.05), the genotype frequency was also higher in GDM than control group(28% vs. 10%, P<0.05). The PPARy2 12A allele frequencies in study and control groups were 6%, 5% respectively. No significant difference between two groups.2. In GDM group, PC-1 121Q allele-carrying subjects showed higher level of fasting plasma glucose, fasting serum insulin, insulin resistance index(P<0.05), and lower insulin sensitivity(P<0.05), compared with K121K individuals. In contrast, no significant difference in any of the measured variables was observed between PPARy2 12A allele-carrying subjects and P12P individuals.3. In GDM groups, the deleterious effects of the PC-1 X121Q genotype on insulin sensitivity dependent upon the coexistence of the PPARy2 P12P genotype, and no deleterious effect of PC-1 X121Q genotype was observed among PPARy2 X12A carriers.Conclusions1. Both PC-1 K121Q and PPARy2 P12A polymorphisms exist in Han nationality women in Tianjin and Hebei province of China.2. PC-1 K121Q variant correlates with the pathogenesis of GDM., suggesting that PC-1 121Q allele is a susceptible gene to GDM. The PPARy2 P12A variant does not associate with GDM significangly.3. In GDM patients, the PC-1 K121Q variant has independent and adverse effect on causing IR. IR of PC-1 121Q allele-carrying subjects was more severe than PC-1 K121K individuals.4. PPARy2 P12A variant may modulate insulin sensitivity by gene-gene interaction with PC-1 K121Q. The results indicate that genetic epistasis between common polymorphic variants does play a role in determining the individual susceptibility to IR.
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