The Relationship Between OPRMI Gene A118G Polymorphism And Intracranial Hemorrhage In Premature Infans

Background and ObjectiveNeonatal intracranial hemorrhage (Intracranial hemorrhage, ICH) is a kind ofserious brain damage disease in neonate. It is more common in premature infants, thesmaller the gestational age, the higher the occurrence rate. Those survivors often haddifferent types and levels neurologic sequelae. In recent years, along with thedevelopment of medicine, the survival rate of the premature infants was greatlyincreased.As a result, the occurrence of ICH continued unabated.The incidence of ICH was associated with premature infant’s anatomical andphysiological features, a variety of perinatal risk factors, as well as manyinflammatory reaction and endogenous mediator, especially the release of the studyon the mechanism of neuropeptide and cerebral vascular disease has been paid moreand more attention. Studys found opioid and opioid receptor system played a veryimportant role in the pathophysiologic process of ischemic stroke in adult.Clinical observation found that premature infants with the same risk factors didnot all have intracranial hemorrhage. The occurrence of ICH had individualdifference. Genetic background is one of the major causes of individual differences.Previous study found that platelet activating factor PAF-AH gene Val279Phe singlenucleotide polymorphisms was associated with the occurrence of ICH. Basing on that, we tried to look for other relative gene with occurrence of ICH.μ opioid receptor (OPRMI) A118G polymorphism was related with asusceptibility to some diseases and diversity of drug response, while whatrelationship between it and ICH in premature infants had not been reported. So weintended to explore the relationship with the OPRMI gene A118G polymorphismwhich was closely related to nervous and mental diseases, and intracranialhemorrhage in this study,hoping for providing the effective prevention and treatmentmethods of ICH.Materials and methods1The research objects and groupingThe present study was conducted between July2011and March2013in theNeonatal Intensive Care Unit (NICU) of the First Affiliated Hospital of ZhengzhouUniversity, Zhengzhou, China. Preterm infants with ICH were enrolled into thepresent study as ICH group, and preterm infants without ICH were enrolled asnon-ICH group simultaneously.Intracranial hemorrhage were divided into4levels.2Genetic polymorphism detectionThe method of PCR-RFLP was used to detect OPRMI A118G polymorphism. Atlast, using DNA sequencing technology to detect the genetypes of the OPRM1geneAl18G polymorphism.3Statistical analysisStatistical analyses were performed using the SPSS version19.0. Usingindependent samples t test for gestational age and birth weight comparation. HardyWeinberg equilibrium of a goodness of fit test，comparation of each group’s genotypeand allele distribution, Comparison of gender were analyzed by chi square test,P<0.05was considered statistically significant. Results1General resultICH group (n=167)，male99cases, female68cases,mean age (33.59±1.95)weeks, the average birth weight (1849±578) g; non-ICH group (n=163),male91cases, female72cases,mean age (33.98±1.63) weeks, the average birth weight (1849±578) g. There was no significant difference between the gender, birth weight of thetwo groups.2OPRMI A118G genotype, allele frequency of two groupsThere are two alleles(A、G) and three genotypes (A/A、A/G、G/G) of OPRMIgene. In ICH group, the number of wild type A118homozygous (A/A)were73(43.7%), mutant heterozygous (A/G)82(49.1%) and mutant G118homozygous (G/G)12(7.2%). The frequencies of A、G allel were68.3%and31.7%, respectively.Innon-ICH group, the number of wild type A118homozygous (A/A) were89(54.6%)，mutant heterozygous (A/G)68(41.7%) and mutant G118homozygous (G/G)6(3.7%).The frequencies of A、G allel were75.5%and24.5%, respectively. There was nosignificant difference of frequences distribution of OPRM1gene A118Gpolymorphism between two groups (χ2=4.839, P=0.089), There was a significantdifference of positive rate of wild-type A/A and mutant-type (A/G+G/G) between twogroups,(χ2=3.913, P=0.048), so allel of G was (χ2=4.22, P=0.040, OR=1.549,95%CI:1.003～2.391). It indicates that OPRM1118G allel has positive correlation with ICH,and it can increases the risk of occurrence of ICH. There is no difference of genotypesand alleles frequencies between OPRM1Gene A118G polymorphism and sex in ICH(χ2=0.300, P=0.58; χ2=0.843, P=0.358). There is no difference between OPRM1Gene A118G polymorphism and the degree of hemorrhage in ICH (χ2=2.418,P=0.342; χ2=0.160, P=0.689).Conclusions1. OPRM1Gene A118G polymorphism has the relationship with intracranialhemorrhage in premature infants. 2. OPRM1Gene A118G may be a sensitive gene which leads the ICH to occur. Gallele was positively correlated with the occurrence of ICH,and the mutation mayincrease the risk of ICH.3. There is no difference between OPRM1Gene A118G polymorphism and sex inICH.4. There is no difference between OPRM1Gene A118G polymorphism and thedegree of hemorrhage in ICH.