Evidence for association of the rs605059 polymorphism of HSD17B1 gene with recurrent spontaneous abortions

Abstract Objective: To investigate whether the missense rs605059 polymorphism of HSD17B1 gene, which is expressed mainly in the placenta, is associated with recurrent spontaneous abortions (RSA). Methods: This study group consisted of 138 women with three or more unexplained spontaneous abortions, before the 20th week of gestation, with the same partner, while 140 healthy women served as controls. To genotype the individuals, we used the polymerase chain reaction-restriction fragment length polymorphism method. Results: The genotyping of the rs605059 polymorphism revealed the frequencies 0.22, 0.45 and 0.33, for AA, GA and GG genotypes, respectively, for the patient group and 0.37, 0.41 and 0.22, respectively, for the control group. The A allele frequencies were 0.44 and 0.57 for the patient and control group, respectively, and the G allele frequencies were 0.56 and 0.43 for the patient and control group, respectively. Statistical analysis of the results indicated the existence of significant differences in genotype and allele frequencies between the two groups. Conclusion: The rs605059 polymorphism of the HSD17B1 gene is associated with increased risk of RSA in our Caucasian Greek population. Thus it could be used as a prognostic genetic marker for RSA.

[1]  B. Tycko,et al.  Polymorphisms in HSD17B1: Early Onset and Increased Risk of Alzheimer's Disease in Women with Down Syndrome , 2012, Current gerontology and geriatrics research.

[2]  R. Vihko,et al.  Two 17β-hydroxysteroid dehydrogenases (17HSDs) of estradiol biosynthesis: 17HSD type 1 and type 7 , 1999, The Journal of Steroid Biochemistry and Molecular Biology.

[3]  M. Beckmann,et al.  Polymorphisms in estrogen metabolism and estrogen pathway genes and the risk of miscarriage , 2009, Archives of Gynecology and Obstetrics.

[4]  Y. Saijo,et al.  A polymorphism in the CYP17 gene relates to the risk of recurrent pregnancy loss. , 2003, Molecular human reproduction.

[5]  S. Daya.  Issues in the etiology of recurrent spontaneous abortion. , 1994, Current opinion in obstetrics & gynecology.

[6]  E. Reinmaa,et al.  Polymorphisms in ESR1, ESR2 and HSD17B1 genes are associated with fertility status in endometriosis , 2011, Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology.

[7]  M. Stephenson.  Frequency of factors associated with habitual abortion in 197 couples. , 1996, Fertility and sterility.

[8]  D D Baird,et al.  Incidence of early loss of pregnancy. , 1988, The New England journal of medicine.

[9]  Liping Cao,et al.  Polymorphisms in genes HSD17B1 and HSD17B2 and uterine leiomyoma risk in Chinese women , 2012, Archives of Gynecology and Obstetrics.

[10]  E. Albrecht,et al.  Actions of placental and fetal adrenal steroid hormones in primate pregnancy. , 1995, Endocrine reviews.

[11]  P. Bork,et al.  A method and server for predicting damaging missense mutations , 2010, Nature Methods.

[12]  Y. Shih,et al.  Polymorphisms in steroidogenesis genes, sex steroid levels, and high myopia in the Taiwanese population , 2011, Molecular vision.

[13]  N. Kim,et al.  Association study of vascular endothelial growth factor polymorphisms with the risk of recurrent spontaneous abortion. , 2010, Fertility and sterility.

[14]  B. Ponder,et al.  Human familial and sporadic breast cancer: analysis of the coding regions of the 17β-hydroxysteroid dehydrogenase 2 gene (EDH17B2) using a single-strand conformation polymorphism assay , 1994, Human Genetics.

[15]  S. Agrawal,et al.  An update in recurrent spontaneous abortion , 2005, Archives of Gynecology and Obstetrics.

[16]  L. Noble,et al.  Endocrinology of recurrent pregnancy loss. , 2006, Seminars in reproductive medicine.

[17]  N. Stefanakis,et al.  Evidence for association of the G1733A polymorphism of the androgen receptor gene with recurrent spontaneous abortions. , 2008, Fertility and sterility.

[18]  Shirley A. Miller,et al.  A simple salting out procedure for extracting DNA from human nucleated cells. , 1988, Nucleic acids research.

[19]  Vladimir N Uversky,et al.  Intrinsically disordered proteins from A to Z. , 2011, The international journal of biochemistry & cell biology.

[20]  M. Stephenson,et al.  Evaluation and management of recurrent early pregnancy loss. , 2007, Clinical obstetrics and gynecology.

[21]  Zsuzsanna Dosztányi,et al.  ANCHOR: web server for predicting protein binding regions in disordered proteins , 2009, Bioinform..

[22]  S. Fisher,et al.  Implantation and the survival of early pregnancy. , 2001, The New England journal of medicine.

[23]  Jian Ye,et al.  Primer-BLAST: A tool to design target-specific primers for polymerase chain reaction , 2012, BMC Bioinformatics.

[24]  S. Henikoff,et al.  Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm , 2009, Nature Protocols.

[25]  J. Long,et al.  Interaction of soy and 17&bgr;-HSD1 gene polymorphisms in the risk of endometrial cancer , 2007, Pharmacogenetics and genomics.

[26]  Burkhard Rost,et al.  ISIS: interaction sites identified from sequence , 2007, Bioinform..

[27]  P. Kuo,et al.  Quantitative trait analysis suggests polymorphisms of estrogen-related genes regulate human sperm concentrations and motility. , 2011, Human reproduction.

[28]  D. Altshuler,et al.  Haplotype analysis of the HSD17B1 gene and risk of breast cancer: a comprehensive approach to multicenter analyses of prospective cohort studies. , 2006, Cancer research.