Association study of the three functional polymorphisms (TAS2R46G>A, OR4C16G>A, and OR4X1A>T) with recurrent pregnancy loss
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This study was purposed to investigate whether genetic polymorphisms in the function of stop-gain are associated with a fetal or placental development play roles and a development of idiopathic recurrent pregnancy loss (RPL) in Korean females. Three stop-gain polymorphisms were selected using next-generation sequencing screening, which allows for the rigorous examination and discovery of previously uncharacterized stop-gain genes and stop-gain expression profiles. Accordingly, we investigated the association of stop-gain polymorphisms in Korean women with RPL. Three functional polymorphisms in the TAS2R46G>A (rs2708381), OR4C16G>A (rs1459101), and OR4X1A>T (rs10838851) genes were genotyped using polymerase chain reaction (PCR)—restriction fragment length polymorphism assays and real-time PCR analysis. We determined that the OR4C16G>A polymorphism was associated with idiopathic RPL in Korean women (Adjusted odds ratio [AOR] 1.782; 95% confidence interval [CI] 1.004–3.163; P = 0.048, and AOR 1.766; 95% CI 1.020–3.059; P = 0.042). In addition, the prevalence of RPL was increased in women with the OR4C16GA + AA genotype and blood coagulation measures of prothrombin time (PT) > 10.4 s (AOR 8.292; 95% CI 2.744–25.054). We suggest that the OR4C16G>A polymorphism might serve as a clinically useful biomarker for the development, prevention, and prognosis of RPL.
KeywordsNext-generation sequencing (NGS) Stop gain mutation Nonsense mutation Polymorphism Recurrent pregnancy loss (RPL)
This study was partly supported by a grant of the Korea Healthcare Technology R&D Project (HI15C1972010015), Ministry for Health, Welfare & Family Affairs, Republic of Korea.
CSR and NKK designed and directed the whole project. EHA, JHK, and WSL collected the blood samples from recurrent pregnancy loss patients and control subjects. CSR and JHS performed the experiments, collected the results, and analyzed the data. NKK and EHA discussed and interpreted the data and results. CSR and JHS wrote the first draft of the manuscript. NKK, JOK, DK and CSR revised the paper. All authors contributed to and approved the final manuscript.
Compliance with ethical standards
Conflict of interest
Chang Soo Ryu, Jung Hyun Sakong, Eun Hee Ahn, Jung Oh Kim, Daeun Ko, Ji Hyang Kim, Woo Sik Lee and Nam Keun Kim declare that they have no conflict of interest.
This study had been approved by the Institutional Review Board of CHA Bundang Medical Center (IRB number: BD2010‑123D) and written informed consent was provided by all patients.
- Abel BS, Shaw ND, Brown JM, Adams JM, Alati T, Martin KA, Pitteloud N, Seminara SB, Plummer L, Pignatelli D et al (2013) Responsiveness to a physiological regimen of GnRH therapy and relation to genotype in women with isolated hypogonadotropic hypogonadism. J Clin Endocrinol Metab 98:E206–E216CrossRefGoogle Scholar
- Bhuiyan ZA, Momenah TS, Gong Q, Amin AS, Ghamdi SA, Carvalho JS, Homfray T, Mannens MM, Zhou Z, Wilde AA et al (2008) Recurrent intrauterine fetal loss due to near absence of HERG: clinical and functional characterization of a homozygous nonsense HERG Q1070X mutation. Heart Rhythm 5:553–561CrossRefGoogle Scholar
- Cameron EL (2014) Pregnancy and olfaction: a review. Front Psychol 5:67Google Scholar
- Chihara M, Yoshihara K, Ishiguro T, Yokota Y, Adachi S, Okada H, Kashima K, Sato T, Tanaka A, Tanaka K et al (2015) Susceptibility to male infertility: replication study in Japanese men looking for an association with four GWAS-derived loci identified in European men. J Assist Reprod Genet 32:903–908CrossRefGoogle Scholar
- Choi YS, Kwon H, Kim JH, Shin JE, Choi Y, Yoon TK, Choi DH, Kim NK (2011) Haplotype-based association of ACE I/D, AT1R 1166A>C, and AGT M235T polymorphisms in renin-angiotensin-aldosterone system genes in Korean women with idiopathic recurrent spontaneous abortions. Eur J Obstet Gynecol Reprod Biol 158:225–228CrossRefGoogle Scholar
- Hummel T, Landis BN, Huttenbrink KB (2011) Smell and taste disorders. GMS Curr Top Otorhinolaryngol Head Neck Surg 10:Doc04Google Scholar
- Saxena P, Misro MM, Roy S, Chopra K, Sinha D, Nandan D, Trivedi SS (2008) Possible role of male factors in recurrent pregnancy loss. Indian J Physiol Pharmacol 52:274–282Google Scholar
- Siasi E, Aleyasin A (2016) Four single nucleotide polymorphisms in INSR, SLC6A14, TAS2R38, and OR2W3 genes in Association with Idiopathic Infertility in Persian Men. J Reprod Med 61:145–152Google Scholar