| IntrodutionHypoxia-inducible factor-1(hypoxia-inducible factor-1,HIF-1) are currently found that it is a transcription factor only playing a specific activity under the hypoxic status.In 1992,Semenza et al firstly found it in Hep3B cell nuclear of the hypoxic liver cell carcinoma cell.HIF-1 exists in mammals and human,and is a heterodimer composing ofαandβsubunit.HIF-1αis only subunit to regulate oxygen.In case of hypoxia,it can demonstrate biological activity.It main combine with the HIF-1 binding site point(5'-TACGTG CT-3 ') on the hypoxia response element(hypoxia response element,HRE) of target gene,and activate the transcription of target genes,exert a wide range of biological functions,including participating in angiogenesis,energy metabolism,red blood cell production,cell proliferation and survival,vascular remodeling,as well as vasomotor response.Encoding HIF-1αgene is located in 14 chromosome q21-24,the region is rich in single nucleotide polymorphism.Now,NCBI has released the 238 SNP loci,more studies are coding region of SNP sites.The study found that single nucleotide polymorphisms about this region can affect protein expression and function.In foreign, the research focused on the relation of genetic polymorphism of HIF-1αand a variety of tumors(such as urinary,digestive,reproductive system tumor),and also had reported that they were closely related to diabetes mellitus,myocardial infarction and ischemic non-traumatic osteonecrosis of the femoral head,and the other diseases.In addition,the study found that HIF-1αis closely related with cerebral ischemia.It plays an important role to defend cerebral ischemia.At home and abroad,it doesn't report relation of HIF-1αgene polymorphism and cerebral hypoxic-ischemic disease.This study chose HIF-1αgene rs2057482 locus..It investigated the distribution of gene frequencies in Liaoning Han and Guangxi Zhuang populations,and probe relation of rs2057482 single nucleotide polymorphism and cerebral infarction.It proposes of providing valuable reference data for human genetics,clinical medicine,as well as forensic science.Materials and Methods1.259 cases and 191 cases of venous blood were collected unrelated healthy blood donors from Han and Guangxi Zhuang in Liaoning.159 cases of venous blood was collected from patients of cerebral infarction in Liaoning Affiliated Hospital of Traditional Chinese Medicine University.The ten DNA samples of core families were provided by department of Forensic Serology China Medical University.2.The genotyping frequencies of HIF-1αgene rs2057482 locus in Liaoning Han, Guangxi Zhuang nationalities and the patients of cerebral infarction were studied by the method of bi-directional allele specific amplification(Bi-ASA),and using this method was also applied to family investigation.3.The allelic and genotype frequencies of HIF-1αgene rs2057482 locus were calculated by the direct count method.Hardy-Weinberg equilibrium tested whether the study groups were representative.It analyzed the genetic distributions differences in different populations,control and case group using SPSS15.0 software.The heterozygosis (H),polymorphic information content(PIC),discrimination power(DP) and excluding probability of paternity(EPP) were calculated according to the literature.ResultsTwo alleles and three genotypes of HIF-1αgene rs2057482 locus were detected in three populations.In Liaoning Han populations,the frequencies of two alleles C and T were 0.8301 and 0.1699,respectively.Three genotypes CC,CT and TT were detected.Their frequencies were 0.6873,0.2857 and 0.0270,respectively.In Guangxi Zhuang population,the frequencies of two alleles C and T were 0.9031 and 0.0969,respectively. Three genotypes CC,CT and TT were detected.Their frequencies were 0.8272,0.1518 and 0.0210,respectively.In patients of cerebral infarction,the frequencies of two alleles C and T were 0.8491 and 0.1509,respectively.Three genotypes CC,CT and TT were detected.Their frequencies were 0.7170,0.2641 and 0.0189,respectively.HIF-1αgene rs2057482 SNP locus was used in the detection of ten father-child-mother families.It did not have genetic variation.DiscussionIn this study,we detected polymorphic distribution of HIF-1αgene rs2057482 locus in Liaoning Han,Guangxi Zhuang populations using the method of bi-directional allele-specific amplification.The result demonstrated that rs2057482 polymorphism exist differences in different national groups.There were significant differences of gene frequency distribution between Liaoning Han and Guangxi Zhuang populations (P＜0.05).This survey results about allele distribution in HIF-1αgene rs2057482 locus compared with other groups' findings.The distribution of gene frequencies was significant difference between the Korean population literature and Guangxi Zhuang population(P＜0.05).The genotype and allele frequencies between Korea and Liaoning Han populations were similar.There was not statistics difference between Korea and Liaoning Han populations(P＞0.05).Now,it was not found about polymorphism distribution of rs2057482 locus in the other populations.Recently,HIF-1αat the role of the central nervous system was constantly known. Marti et al studied mice models of cerebral ischemia.It had shown that:Brain ischemia and hypoxia can lead to increase the expression of HIF-1,activate vascular endothelial growth factor and its receptor gene,caused vessels endothelial cell proliferation in brain tissue,induce angiogenesis and improving nerve damage causing by blood and oxygen supply,but also inhibited the hypoxia-induced apoptosis of neural cells.This physiological mechanism could improve the prognosis of patients with cerebral ischemia.Show that the HIF-1αis closely related with cerebral ischemia,and play an important role in response to cerebral ischemia.Cerebral infarction is common pathological changes of cerebral hypoxic-ischemic disease.Nowadays,it has not studied relationship between HIF-1αpolymorphisms and this disease.This study found that the alleles and genotype frequencies distribution of HIF-1αrs2057482 locus between Liaoning Han health and patients of cerebral infarction were not significant difference(P＞0.05).It suggested that there was difference about HIF-1αrs2057482 locus polymorphism in different populations.According to the survey data,calculate forensic parameters of two groups, Liaoning Han and Guangxi Zhuang.The heterozygosity are 0.564 and 0.350, polymorphic information content are 0.2423 and 0.1597,the power of discrimination are 0.445 and 0.292,the excluding probability of paternity are 0.121 and 0.080 respectively in Han and Zhuang nationalities.The rs2057482 locus of HIF-1αgene is polymorphic,and its power of discrimination falls in moderate which can be applied in forensic practice.Conclusions1.In this study,HIF-1αgene rs2057482 locus has genetic polymorphism between Liaoning Han and Guangxi Zhuang populations,and is in accordance with the Hardy-Weinberg balance.2.The alleles of HIF-1αgene rs2057482 locus are significant different between Liaoning Han and Guangxi Zhuang populations,and are also significant different between Guangxi Zhuang and Korea populations;but are not statistical significance between Liaoning Han and Korea populations.3.HIF-1αgene rs2057482 locus doesn't associated with the occurrence of cerebral disease.4.The rs2057482 locus of HIF-1αgene is polymorphic,and its power of discrimination falls in moderate which can be applied in forensic paternity testing and individual identification.
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