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The Association Between P-selectin Gene Polymorphisms And Plasma Soluble P-selectin Levels In Fujian Han Population

Posted on:2013-01-20Degree:MasterType:Thesis
Country:ChinaCandidate:Y L LuoFull Text:PDF
GTID:2254330392467235Subject:Immunology
Abstract/Summary:PDF Full Text Request
P-selectin is expressed on activated platelets and endothelial cell surface. It fallsoff quickly into plasma to form soluble P-selectin. The SELP gene containsapproximately291SNPs, therefore, it is highly polymorphic. The storage damage ofplatelet is one of the reasons of its short storage life. Platelet storage damage isimpacted by platelet activation, which is indicated by the existence of transmembraneand soluble P-selectin. P-selectin plays an important role in the inflammation,thrombosis, coagulation and fibrinolysis which are resulted from venousthromboembolism, hypertension, coronary heart disease and acute myocardialinfarction and other cardiovascular diseases. Recent studies have shown that thesingle nucleotide polymorphisms of individual P-selectin gene, especially the codingregion missense mutations and haplotype, has significant impact on the level ofsoluble P-selectin and the risk of future relevant diseases.The SNP of P-selectin gene in Val168Met (rs6125), Ser290Asn (rs6131),Asn562Asp (rs6127) and Thr715Pro (rs6136) were analyzed from450Fujian healthyHan people using MALDI-TOF-MS technology, and gene frequencies wereVal168Met: A=0.0022, G=0.9978; Ser290Asn: A=0.2133, G=0.7867; Asn562Asp:A=0.9811, G=0.0189; Thr715Pro: A=1.0000. Gene frequencies of four locus were inHardy-Weinberg equilibrium. Ser290Asn and Asn562Asp are polymorphisms, butVal168Met and Thr715Pro are single. The95%confidence intervals of GGAA,GAAA, GGGA, GAGA, AAAA, AAGA, haplotype frequency were:0.77026(0.74276-0.79776);0.20973(0.18312-0.23635);0.01641(0.00810-0.02471);0.00138(0.00000-0.00380);0.00112(0.00000-0.00330);0.00110(0.00000-0.00327).The rs6125locus gene frequencies of the Fujian Han population (A=0.0022, G=0.9978) and German Caucasians (A=0.0654, G=0.9346) have a significantdifference (P <0.01). The rs6127gene frequencies of the Fujian Han population (A=0.9811, G=0.0189) and the Arab (A=0.6354, G=0.3646) and the German Caucasians (A=0.5818, G=0.4182) have a significant difference (P<0.01). The rs6131genefrequencies of the Fujian Han population (A=0.2133, G=0.7867) and the Arab (A=0.2251, G=0.7749) and the German Caucasians (A=0.2033, G=0.7967) have nosignificant difference (P>0.05). The rs6136gene frequencies of the Fujian Hanpopulation (A=1.0000) and the Arab (A=0.9747, G=0.0253) and the GermanCaucasians (A=0.9042, G=0.0958) and white Americans (A=0.8893, G=0.1107) havea significant difference(P<0.01). Except that Thr715Pro (rs6136) has only onegenotype (AA) that can not be compared, the rest three locus genotypescorresponding soluble P-selectin levels have no significant difference. The plasmaP-selectin levels of GGAA haplotype (Val168-Ser290-Asn562-Thr715) are higherthan other SELP haplotype. Compared with other haplotype, the GGAA (GAAAGGGA, AAAA, AAGA, GAGA) have a significant difference (P<0.05).The preliminary results indicated that: in the investigated four SELP gene SNPs,rs6127and rs6131locus are polymorphic, rs6131locus is most strongest, rs6127locus is the secondary strong, rs6125and rs6136locus are monomorphic; In the SELPgene rs6125-rs6131-rs6127-rs6135haplotype, the haplotypes (allele) frequencies ofGGAA, GAAA and GGGA are up to the level of polymorphism, three alleles ofAAAA, AAGA and GAGA are rare alleles; Han population exhibits a significantdifferent genotype and allele frequency as compared to the reported data either fromwestern or Arab population;The four locus genotypes corresponding solubleP-selectin levels have no significant difference. The plasma P-selectin levels ofGGAA haplotype (Val168-Ser290-Asn562-Thr715) are higher than other SELPhaplotype.
Keywords/Search Tags:P-selectin gene, single nucleotide polymorphism, haplotype, Han, solubleP-selectin
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