title: Polymorphisms in the annexin A5 gene promoter in Japanese women with recurrent pregnancy loss.
abstract: Recent findings have raised the possibility that polymorphisms within the annexin A5 gene (ANXA5) promoter contribute to the etiology of recurrent pregnancy loss (RPL). In our present study, 243 Japanese women who had suffered more than three fetal losses and a group of 119 fertile controls were genotyped for four ANXA5 gene promoter single-nucleotide polymorphisms (SNPs; SNP1-4: g.-467G >A, g.-448A>C, g.-422T>C, g.-373G>A) previously reported to be associated with this disorder. An additional two SNPs located within the 5'-untranslated region of the ANXA5 (SNP5 and 6: g.-302T>G, g.-1C>T) were also evaluated. Our case--control study revealed that the minor allele was significantly more frequent in the RPL group than controls for all six of these SNPs, among which SNP5 showed the highest significance (P= 0.002). As with the M2 haplotype for SNP1-4 (A-C-C-A) for a western population in previous reports, a haplotype comprising all of the minor alleles for SNP1-6 (A-C-C-A-G-T), the third major haplotype in the Japanese population, showed a significantly higher frequency in our current RPL subjects than in controls (P= 0.025). In addition, the second major haplotype (G-A-T-G-G-C) was found to confer a significant risk of RPL (P= 0.036), implicating SNP5 as a major risk determinant for this disease. Our present findings support the hypothesis that genomic variations within the ANXA5 gene upstream region impact upon the disease susceptibility to RPL. Our data indicate that SNP5 is a novel risk factor for this disease in the Japanese population.
authors.affiliation: Division of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Miyamura
authors.forename: Haruki
authors.initials: H
authors.lastname: Nishizawa
authors.forename: Sayuri
authors.initials: S
authors.lastname: Ota
authors.forename: Machiko
authors.initials: M
authors.lastname: Suzuki
authors.forename: Ayaka
authors.initials: A
authors.lastname: Inagaki
authors.forename: Hiromi
authors.initials: H
authors.lastname: Egusa
authors.forename: Sachie
authors.initials: S
authors.lastname: Nishiyama
authors.forename: Takema
authors.initials: T
authors.lastname: Kato
authors.forename: Kanako
authors.initials: K
authors.lastname: Pryor-Koishi
authors.forename: Isao
authors.initials: I
authors.lastname: Nakanishi
authors.forename: Tomio
authors.initials: T
authors.lastname: Fujita
authors.forename: Yuzo
authors.initials: Y
authors.lastname: Imayoshi
authors.forename: Arseni
authors.initials: A
authors.lastname: Markoff
authors.forename: Itaru
authors.initials: I
authors.lastname: Yanagihara
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Udagawa
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kurahashi
mesh_terms: D000026:Abortion, Habitual / Q000453:epidemiology / Q000235:genetics*; D000328:Adult; D017304:Annexin A5 / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D011110:Polymorphism, Genetic / Q000235:genetics*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics
chemical_list: D017304:Annexin A5