The Prevalence Of 4G/5G Polymorphism Of Plasminogen Activator Inhibitor-1(PAI-1) Gene In Gestational Diabetes And Its Association With Plasma Activity

Objective To investigate the prevalence of 4G/5G polymorphism of plasminogen activator inhibitor-1(PAI-1)gene in gestational diabetes(GDM) and its functional significance.Methods We studied 60 gestational diabetes(GDM)patients and 60 normal controls and their newborn infants.Blood pressure,body height and progravid weight of the pregnant women were measured,and then counted out the body mass index(BMI).Blood samples were obtained for DNA analysis. The 4G/5G polymorphic site of the PAI-1 gene promoter region was amplified by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).The plasma PAI-1 activity was detected by synthetic chromogenic substrate assay in all subjects.The birth weights of all the newborns were measured accurately.Results 1.There was a statistically significant difference in the distribution of 4G/5G polymorphism of PAI-1 gene and allele variations among the two groups(P＜0.05).The 4G/4G genotype was more frequent in GDM group than in control group,whereas 5G/5G genotype was less frequent.Among the GDM women,the genotype 4G/4G was 41.7%,4G/5G was 43.3%and 5G/5G was 15.0%.Comparatively,among the control group,the genotype 4G/4G was 20.0%,4G/5G was 51.7%and 5G/5G was 28.3%.In the 4G/4G genotypes subgroup 67.6%were GDM patients and 32.4%were controls,in the 4G/5G were 45.6%and 54.4%,and in the 5G/5G were 34.6%and 65.4%respectively. The 4G allele was more frequent in GDM groups than that of control group(63.3%vs 45.8%,P＜0.01).2.The GDM group had significantly higher plasma PAI-1 activity than that of the controls(0.788±0.066 AU/ml vs 0.713±0.035AU/ml,P＜0.05).Within the GDM group,the plasma PAI-1 activity of 4G/4G genotype was significantly higher than that of the 4G/SG and 5G/5G genotype(P＜0.05).Within the control group,that of the 4G/4G genotype was significantly higher than of the 4G/5G and 5G/5G genotype(P＜0.05).There were significantly different of plasma PAI-1 activity between the same genotypes of the two groups respectively(P＜0.05).3.The progestational BMI of GDM group was significantly higher than that of the controls(23.14±1.93 kg/m~2 vs 21.59±1.59 kg/m~2,p＜0.01).The progestational BMI of genotype 4G/4G was significantly higher than that of 4G/5G and 5G/5G genotype.The proportion of overweight of GDM group was significantly higher than that of controls(36.7%vs 11.7%,P＜0.05).At the same time,the proportion of overweight of genotype 4G/4G was significantly higher than that of 4G/5G and 5G/5G genotype(P＜0.05).The overweight women had significantly higher PAI-1 activity than that of the nomal weight women.The result of multiple liner regression show that the PAI-1 activity were closely correlated with genotype(r=0.582,P＜0.001).4.The newborn weight of the GDM group was significantly bigger than that of the controls(P＜0.01),and that of 4G/4G genotype was significantly higher than 4G/5G and 5G/5G(P＜0.05).The same results could be seen between the GDM and control group(P＜0.05).The result of multiple liner regression show that the body weight of infants were closely correlated with genotypes(r=0.483, P＜0.001).Conclusions 1.The 4G/4G genotype is more frequent in GDM group, suggesting that 4G/4G homozygote is a susceptible gene to GDM in women with Han nationality in Guangxi province of China.2.Compared with the control group,GDM women have higher plasma PAI-1 activity,pregestational BMI and the proportion of overweight.3.The presence of the 4G allele in PAI-1 promoter region of the gene may increase the blood PAI-1 activity.4.PAI-Ⅰgene polymorphism 4G/4G gene and higher blood PAI-1 activity may be correlated with pre-gestational BMI of the woman in pregnant,and then result in the occurrence of GDM.5.The presence of the 4G/4G gene in PAI-1 promoter region of the gene may be correlated with weight gain in newborn of GDM women.