Polymorphisms of the transforming growth factor-beta 1 gene in relation to idiopathic recurrent miscarriage (P6248)

Abstract

Abstract Transforming growth factor, β1 (TGFB1) plays a significant role in the pregnancy outcome. We investigated the association of TGFB1 exon 1 (rs1800471, rs1800470) and promoter region (rs1800469, rs1800468) polymorphisms with recurrent pregnancy loss (RPL) in 675 Tunisian women: 304 women with a history of three consecutive pregnancy loss of unknown etiology with the same partner, and 371 age-matched multiparous control women. TGFB1 genotyping was done by TaqMan assays. Higher minor allele frequency (MAF) for rs1800471 (i.e. +915G/C or R25P) (P < 0.001), but not for rs1800470, rs1800469, or rs1800468 was found in cases compared to controls. Significant difference in the distribution of rs1800471 genotypes was seen between RPL cases and control women, irrespective of the genetic model used. Increased RPL risk was seen with rs1800471 allele C in both heterozygous and even more so in the homozygous state, thus establishing a dose-dependent effect. Haploview analysis revealed differential linkage disequilibrium between TGFB1 SNPs analyzed. TGFB1 haplotypes analysis identified 8 common haplotypes (rs1800471/rs1800470/rs1800469/rs1800468) with three (GTTG, Pc = 0.014; CCTG, Pc = 0.003, and CTCG, Pc = 0.01) being positively associated with RPL, while one (GCCG, Pc = 0.009) was negatively associated with RPL. This study provides the first evidence that TGFB1 genotype is possibly associated with RPL.