Association Of Genetic Polymorphisms In 5, 10-methylenetetrahydrofolate Reductase Gene, Plasminogen Activator Inhibitor-1 Gene With Preterm Birth And Spastic Cerebral Palsy

ObjectiveTo investigate whether Methylenetetrahydrofolate reductase (MTHFR)gene C677T, A1298C and Plasminogen activator inhibitor-1 (PAI-1) gene promoter region 675 4G/ 5G polymorphisms in the infants are associated with Preterm Birth (less than 37 weeks) and Spastic Cerebral Palsy among children with cerebral palsy and impaired children.MethodAccording to their informed consents, A 1:1 Case-control study investigating the relationship of gestational age at delivery and spastic cerebral palsy to MTHFR gene C677T, A1298C and PAI-1 gene promoter region 675 4G/5G polymorphisms measured in peripheral venous blood(1ml). Children were born after spontaneous onset of labor, The conditions of partnership were ages differing less than one month(≦1year), while less than three months(>1year), level of birth hospital, preterm or term infants.Using random numbers,selecting 12 chidren from 162 HIE term infants with cerebral palsy, to match 12 term impaired children. Excluding useless blood, impaired children were 272. (101 preterm impaired children, 171 term impaired children). Among all 265 children with cerebral palsy, 103 of these were preterm (gestational age less than 37 weeks). 265 children with cerebral palsy were from①Center of Neurology and Rehabilitation for Children , First Affiliated Hospital of Anhui Medical University,②Neonate Pediatrics in First Affiliated Hospital of Anhui Medical University,③Maternal and Child Health Institute of Hefei. Impaired Children were from Maternal and Child Health Institute of Hefei.Genotyping was performed using polymerase chain reaction ( PCR) followed by restriction enzyme analysis (PCR-RFLP) technique.Using non-conditional Logistic regression, Distributions of genotypic frequencies in risk of Preterm Birth were examined in preterms compared with term infants with and without cerebral palsy. Distributions of genotypic frequencies in risk of Spastic Cerebral Palsy were examined in cerebral palsy children with and without preterm compared with impaired children with and without preterm. At the same time, case-control groups in cerebral palsy and impaired children were divided separately into two layers(①<32 weeks,②≧ 32weeks&<37weeks)while risk was evaluated.Also children with cerebral palsy were divided separately into spastic diplegia, spastic hemiplegia and spastic quadriplegia, while risk was evaluated.Results1 After controlling for sex, birth weight, gestational age, type of cerebral palsy, age of pregnant mother, birth history, economic status and educational background, In cerebral palsy children and impaired children, The MTHFR-677 TT genotype showed strong positive association with Preterm Birth(P=0.001, P=0.009), In cerebral palsy children(gestational age<32w), TT genotype was positively related with Preterm Birth(P=0.023); Among impaired children(gestational age<32w), TT genotype wasn't significantly related with Preterm Birth, but only six children (gestational age<32w) couldn't interprete the relationship between TT genotype and Preterm Birth. In cerebral palsy children and impaired children(gestational age≧ 32w&<37w), There was strong positive association between TT genotype and Preterm Birth(P=0.005, P=0.009) .There existed no significant association between TT genotype and Spastic Cerebral Palsy.2 After controlling for sex, birth weight, gestational age, type of cerebral palsy, age of pregnant mother, birth history, economic status and educational background, There existed no significant association between MTHFR-1298, PAI-1 promoter region-675 and Preterm Birth, between MTHFR-1298, PAI-1 promoter region-675 and Spastic Cerebral Palsy.3 Preterm Birth was affected by socio-economic status, moderate economic status may prevent Preterm Birth. Perhaps, girls were negatively associated with Spastic Cerebral Palsy.Conclusion1 Probably, The MTHFR-677 TT genotype was positive association with Preterm Birth, while MTHFR-677 TT genotype wasn't significantly related with Spastic Cerebral Palsy. There existed no significant association between MTHFR-1298, PAI-1 promoter region-675 and Preterm Birth, between MTHFR-1298, PAI-1 promoter region-675 and Spastic Cerebral Palsy.2 Preterm Birth was affected by socio-economic status; Perhaps, girls were negatively associated with Spastic Cerebral Palsy.