Evaluation of a gene panel on ovulation induction in pcos patients
Tahereh Javid tajrishi,
1 Seyed ahmad mousavi,
2 Ali asghar akhlaghi,
3 Marzieh shiva,
4 Mehdi totonchi,
5 Parvaneh afsharian,
6,*
1. 1.Department of Molecular Genetics, Faculty of Basic Sciences and Advanced Technologies in Biology, University of Science and culture, Tehran, Iran. 2. Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.
2. 3.Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
3. 4. Department of Epidemiology and Reproductive Health, Reproductive Epidemiology Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.
4. 5. Department of Endocrinology and Female Infertility, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.
5. 2. Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran. 3.Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
6. 2. Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.
Abstract
Introduction
Pcos is the most prevalent endocrine disorder in women and a major cause of anovulatory infertility. treatment of pcos aims to restore ovulation which consists of clomiphene citrate (cc), aromatase inhibitors (ais), recombinant fsh (rfsh) and insulin sensitizers (such as metformin). drug metabolizing genes polymorphisms might alter the function of drug-metabolizing enzymes or targets leading to a different response to their ovulation induction effects. the aim of this study was to investigate a pharmacogenetic panel for drug response prediction in pcos patients.
Methods
A total of 12 single nucleotide polymorphisms in four genes [cyp2d6, cyp19a1, fshr, and stk11] were investigated in 79 pcos patients (143 cycles) and 87 healthy women with normal oogenesis (133 cycles) who have been in controlled ovulation induction cycles and were taken clomiphene citrate or letrozole in each cycle.
all the ovulation induction cycles (276 cycles) were categorized based on follicle count with a minimum size of 15 mm confirmed by ultrasonography. bioinformatics and statistical analysis were performed in r environment and stata software to evaluate the relationship between significant haplotypes and drug response.
Results
According to haplotype and regression analysis, in pcos patients with a variant haplotype in cyp19a1 gene (rs2414096-a/(ttta) 12 tandem repeats/tct trinucleotide insertion/rs700519-c ) a significant 1.4-fold decrease in average number of follicles with a minimum size of 15 mm was detected in comparison with the control group (p<0.05). nevertheless this relationship was not influenced by the drug types.
Conclusion
No significant associations between ovulation induction and polymorphisms of cyp2d6, cyp19a1, fshr, and stk11 genes were confirmed in pcos patients comparing to healthy controls. however, average number of follicles larger than 15 mm was significantly lower in patients with cyp19a1 polymorphism in comparison with the control group (p<0.05).
Keywords
Pcos, ovulation induction, polymorphism, haplotype
