Association Of The TGF-β1 Gene Polymorphism With The Recurrent Spontaneous Abortion

Objective Transforming growth factor-β1 (TGF-β1) is a multifunctional cytokine and play an important role in the process of many diseases . We examined the four SNPs of TGF-β1 gene(SNP-800G/A,SNP-509C/T polymorphisms in promotor region and the SNP+869T/C,SNP+915G/C polymorphisms in exon 1 region ) to analyze the association of TGF-β1 gene polymorphisms and haplotype with the recurrent spontaneous abortion (RSA) in Ningxia .Methods 228 patients of RSA were from NingXia genetic laboratory with an average age of 27.89±4.42. 213 normal pregnancy women with an average age of 27.56±3.60 came from Maternal and Child Health Hospital as control group. The Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) were used to examine the genotype distribution and allele frequency of TGF-β1 gene. SPSS13.0 software was used to calculate the chi-square result and estimate the risk of RSA.We analyzed Hardy-Weinberg balance, linkage disequilibrium and haplotype by software SHEsis.Results①The genotype distribution of the 4 SNPs in TGF-β1 gene reached Hardy-Weinberg equilibrium.②The genotype frequency of TT at position-509 in patients are significantly higher comparing with the healthy controls(P=0.028,OR=1.651). The CC and CT genotype distribution frequeny of TGF-β1 gene in SNP-509 were no different . The allele T at position-509 in patients are significantly higher than the healthy controls, and allele C in patients are lower than the healthy controls(P=0.022,OR=1.363;P=0.022,OR=0.734).The frequencies of genotype and allele of TGF-β1 gene at position-800, +869, +915 were not significantly different between the two group(P>0.05).③Each pair of four SNPs in TGF-β1 gene were linkage disequilibrium(D'>0.8).④Among the haplotypes established by the 4 SNPs, there were seven kinds of protective haplotypes significantly different between the two group (P<0.05, OR<1), and three kinds of rise haplotypes also have significant difference (P<0.05, OR>1).Conclusions (1) The genotype distribution and allele frequencies of TGF-β1 gene SNP-800, SNP+869, SNP+915 are not significantly different between the two groups. These polymorphisms locus may not associated with the susceptibility of RSA in NingXia female. (2) The polymorphism of TGF-β1 gene at the promoter-509C/T were the possible risk factors associated with the recurrent spontaneous abortion in NingXia female.The patients with genotype TT and allele T of TGF-β1 gene SNP-509 were higher risk factors. (3) Each pair of four SNPs were linkage disequilibrium.(4)Seven protective haplotypes and three rise haplotypes established by the four SNPs of TGF-β1 gene were significantly different between the two group. Objective To study the frequencies of allele and genotype distribution of transforming growth factor-β1 (TGF-β1) gene promoter-800G/A,-509C/T and the first exon+869T/C,+915G/C polymorphisms in the Hui and Han people in Ningxia Province, and to analyze the distributions of TGF-β1 gene polymorphism among different places and race.Methods The gene TGF-β1-800G/A,-509C/T,+869T/C and +915G/C polymorphismswere examined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods in 210 hui and 308 han healthy adults.Results TGF-β1-800G/A,-509C/T,+869T/C and +915G/C genotypes frequencies were -800(GG:97.62%;GA:2.38%;AA:0%;G:98.81%;A:1.19%);-509(CC:21.90%;CT:56.67%;TT:21.43%;C:50.24%;T:49.76%);+869(TT:25.24%;CT:52.38%;CC:22.38%;T:51.43%;C:48.57%);+915(GG:98.10%;GC:1.90%;CC:0%;G:99.04%;C:0.96%) of Ningxia Hui ethnic,respectively.TGF-β1-800,-509,+869 and +915 genotypes frequencies were-800(GG:99.03%;GA:0.97%;AA:0%;G:99.52%;A:0.48%);-509(CC:27.27%;CT:50.97%;TT:21.75%;C:52.76%;T:47.24%);+869(TT:30.52%;CT:48.05%;CC:21.43%;T:54.55%;C:45.45%);+915(GG:99.03%;GC:0.97%;CC:0%;G:99.51%;C:0.49%) of Ningxia Han ethnic,respectively.The phenotype frequency and allele gene frequency of TGF-β1 gene were not significantly different between the Hui and Han ethnic in Ningxia (P>0.05). The phenotype frequency and allele gene frequency of TGF-β1gene were not significantly different between the female and male people in Ningxia. (P>0.05). Conclusion The four SNPs of TGF-β1 genes distribution in the Hui and Han ethnic of Ningxia is not significantly different..The distributions of TGF-β1 genes are significantly different among the other places and ethnic population.