The plasminogen activator inhibitor-1 (PAI-1) gene -844 A/G and -675 4G/5G promoter polymorphism significantly influences plasma PAI-1 levels in women with polycystic ovary syndrome.
Mutations in the plasminogen activator inhibitor-1 (PAI-1) gene, along with increased PAI-1 levels, have been implicated in the pathogenesis of polycystic ovarian syndrome (PCOS). We investigated a possible influence of the promoter polymorphism (-844 A/G and -675 4G/5G) in the PAI-1 gene on plasma PAI-1 levels in 126 PCOS patients and 97 healthy controls. Levels of total testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH), fasting plasma glucose (FPG), fasting insulin, and PAI-1 were measured, and body mass index (BMI), waist-to-hip ratio (WHR), LH/FSH ratio, and homeostasis model assessment for insulin resistance (HOMA-IR) were calculated. PAI-1 -675 4G/5G and -844 A/G gene polymorphisms were also performed. Total testosterone, fasting insulin, and PAI-1 levels; BMI, LH/FSH, and HOMA-IR were significantly higher in PCOS patients than controls (P < 0.05). The odds ratio of 4G/4G genotype, 4G allele, and the combination genotype of 4G/4G and -844 A/A were 2.49 (95% confidence interval (CI), 1.4-4.44), 2.1 (95% CI, 1.43-3.08), and 2.9 (95% CI, 1.41-5.98), respectively, (P < 0.001). In the PCOS group, the PAI-1 level of the A/A was significantly higher than that of the A/G or G/G genotype, similarly was 4G/4G genotype compared with 4G/5G or 5G/5G genotype. The plasma PAI-1 levels of the combination of the PAI-1 -844 A/A and -675 4G/4G or 4G/5G genotypes, or the coadunation of 4G/4G and -844 non-G/G (A/A + A/G) genotypes were significantly high in PCOS women compared with controls. A trend to a positive interaction between PAI-1 -675 4G/5G and -844 A/G gene polymorphism may elevate plasma PAI-1 levels and hypofibrinolysis, which is probably an important hereditary risk factor in PCOS.
Lin
Sun
S
Department of Reproductive Endocrinology, The First Affiliated Hospital of Harbin Medical University, No. 23 YouZheng Street, Harbin, 150001 Heilongjiang, China. sunlin520@hotmail.com
Huiya
Zhang
Z
Bo
Liu
L
Wei
Wei
W
Yongmei
Guan
G
D000328:Adult; D015992:Body Mass Index; D016022:Case-Control Studies; D005260:Female; D005342:Fibrinolysis / Q000235:genetics; D005640:Follicle Stimulating Hormone / Q000097:blood; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D007986:Luteinizing Hormone / Q000097:blood; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood* / Q000235:genetics*; D011085:Polycystic Ovary Syndrome / Q000097:blood* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D011401:Promoter Regions, Genetic / Q000235:genetics; D049629:Waist-Hip Ratio; D055815:Young Adult
D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone