Study On The Association Between PAI-1 4G/5G Gene Polymorphism With Gestational Diabetes Mellitus And Vasculopathy

BackgroundGestational diabetes mellitus(GDM) is defined as abnormality of glucosemetabolism that occurs or is detected for the first time during pregnancy. Not onlyGDM dosen't only increase the risk of adverse outcomes for both mother and infant, butalso may increase the risk of type 2 diabetes mellitus(T2DM) and vasculardysfunction after parturition. GDM is characterized as insulin resistance(IR).Several reports indicate that plasminogen activitor inhibitor-1 (PAI-1) 4G/5G genepolymorphism may adversely influence insulin sensitivity and lead to insulinresistance(IR) associated with T2DM, obesity or cardiovascular disease by inhibitingPAI-1 activity. Some investigations reveal PAI-1 4G/4G gene type may contributeto the pathogenesis of T2DM or cardiovascular disease. But study on the relationshipbetween the polymorphism and GDM with vascular dysfunction is still unclear.ObjectiveIn this study, we want to investigate the association between PAI-1 4G/5G genepolymorphism with the people with GDM in Han nationality women in Tianjinand Hebei province of China, to find susceptible gene or protect gene related toGDM. Meanwhile, we make research about the risk of vascular dysfunction withGDM and its association with PAI-1 4G/5G gene polymorphism.Methods150 unrelated subjects were divided into two groups, women with GDM andpregnant women with normal glucose tolerance(n=75 for each group). Caseswould be warranted to exclude the influence of insulin sensitivity andvasculopathy, such as hypertensive disorder complicating pregnancy, chronichypertension, heart disease, hyperlipemia and disease of hematological system.Comparing the age, parities and gestational weeks of both groups and find that there is no difference statistically. The genotypes of PAI-1 4G/5G variants weredetected by polymerase chain reaction (PCR) assay. The clinical data were alsoanalyzed.Results1. The PAI-1 4G/4G, 4G/5G, 5G/5G gene types all can be detected in woman withGDM and control group. 4G/4G genotype frequency was bigger in women withGDM compared with that in control group(47% vs.24%, P＜0.05), the 4G allelefrequency was also higher in GDM than control group(63% vs.51%, P＜0.05).2. The BMI ofprogestation, blood pressure, fasting blood glucose, fasting insulin,insulin resistance index, fibrinogen, triglyceride, total cholesterol of GDM groupwere higher than those of control group(P＜0.05), while insulin function, insulinsensitivity index, activated partial thromboplastin time of GDM group were lowerthan those of control group(P＜0.05).3. In GDM group, PAI-1 4G/4G genetype-carrying subjects showed higher levelof BMI of progestation, D-dimer compared with 5G/5G genetype-carryingsubjects and higher level of fasting serum insulin, insulin resistance index,fibrinogen, triglyceride, total cholesterol compared with 5G/5G and 4G/4Ggenetype-carrying subjects (P＜0.05).Conclusions1. PAI-1 4G/5G polymorphism exists in women with Han nationality in Tianjinand Hebei province of China.2. PAI-1 4G/5G polymorphism correlates with the pathogenesis of GDM.,suggesting that PAI-1 4G/4G homozygotes is a susceptible gene to GDM.3. In GDM patients, IR of PAI-1 4G/4G gene type-carrying subjects was moresevere than PAI-1 5G/5G individuals. This finding can bring a guidance forprevention and cure of GDM, as well as to anticipate the severity of disease. 4. GDM patients get more risk of developing vasculopathy compared withpregnant women with normal glucose tolerance.5. In GDM patiens, PAI-1 4G/4G gene type is one of high risk genetic factors thatcontributed to develop vasculopathy.