TY - JOUR
T1 - Association of novel stop-gained leukaemia inhibitory factor receptor gene (rs121912501) variant, leukaemia inhibitory factor and ovarian steroids with unexplained infertility among Pakistani women
AU - Ali, Rabiya
AU - Iqbal, Mehir un Nisa
AU - Rehman, Rehana
AU - Khan, Taseer A.
N1 - Funding Information:
Special thanks to the Department of Biological and Biomedical sciences Aga Khan University, Karachi, and Dr Shaheen Eijaz, Urban Hospital North Karachi, helped a lot in the recruitment of fertile women and collection of their samples.
Publisher Copyright:
© 2021 John Wiley & Sons Ltd
PY - 2021/7
Y1 - 2021/7
N2 - Aims and Objectives: Embryo implantation is a complex process that requires sequential steps at the interface of embryo interaction with decidual endometrium. Many women after experiencing multiple attempts of assisted reproductive techniques fail to get implantation because of instability of leukaemia inhibitory factor and leukaemia inhibitory factor receptor-signal transducer and activator of transcription factor 3 (LIF-LIFR STAT3) signalling cascade. Therefore, this study explores the association of ovarian steroids, LIF and LIFR stop-gained variant using the tetra primer amplification refractory mutation system-polymerase chain reaction (TARMS-PCR) with unexplained infertility (UEX-IF) among Pakistani women. Materials and Methods: This is a case-control study, a total of 81 unexplained infertile women and 162 fertile controls (with age and BMI matched) were inducted. Serum estradiol, progesterone and LIF were determined using enzyme-linked immunosorbent assay (ELISA). T-ARMS-PCR was designed using Primer 1 software. Genomic DNA was extracted from peripheral blood and amplified using T-ARMS-PCR followed by sequencing for validation and comprehensive concordance. Results: This study established differences in LIF levels (χ2 = 9.857, P <.05) between patients and controls as well as explored the decreased LIF significantly raised the risk of UEX-IF (OR = 2.316; 95% CI = 1.214, 4.416). Progesterone (P) was significantly associated with UEX-IF between fertile and infertile counterparts (χ2 = 20.347, P <.05). It was also observed that increased Progesterone reduced the risk of UEX-IF (OR = 0.306; 95% CI = 0.166, 0.567). A rapid and inexpensive method for genotyping novel LIFR gene polymorphism through T- ARMS-PCR was successfully developed. LIFR gene SNP (rs121912501) had significant association (χ2 = 200.681, P <.05) with UEX-IF. LIFR rs121912501 “TT” genotype (OR = 5.417; 95% CI = 1.868, 15.709) and “CT” genotype (OR = 3.104, 95% CI = 1.586,6.076) were at increased risk of infertility. Conclusion: UEX-IF can be caused by LIFR gene variation irrespective of increased P. It may open the doors for the discovery of new management plans for infertile women.
AB - Aims and Objectives: Embryo implantation is a complex process that requires sequential steps at the interface of embryo interaction with decidual endometrium. Many women after experiencing multiple attempts of assisted reproductive techniques fail to get implantation because of instability of leukaemia inhibitory factor and leukaemia inhibitory factor receptor-signal transducer and activator of transcription factor 3 (LIF-LIFR STAT3) signalling cascade. Therefore, this study explores the association of ovarian steroids, LIF and LIFR stop-gained variant using the tetra primer amplification refractory mutation system-polymerase chain reaction (TARMS-PCR) with unexplained infertility (UEX-IF) among Pakistani women. Materials and Methods: This is a case-control study, a total of 81 unexplained infertile women and 162 fertile controls (with age and BMI matched) were inducted. Serum estradiol, progesterone and LIF were determined using enzyme-linked immunosorbent assay (ELISA). T-ARMS-PCR was designed using Primer 1 software. Genomic DNA was extracted from peripheral blood and amplified using T-ARMS-PCR followed by sequencing for validation and comprehensive concordance. Results: This study established differences in LIF levels (χ2 = 9.857, P <.05) between patients and controls as well as explored the decreased LIF significantly raised the risk of UEX-IF (OR = 2.316; 95% CI = 1.214, 4.416). Progesterone (P) was significantly associated with UEX-IF between fertile and infertile counterparts (χ2 = 20.347, P <.05). It was also observed that increased Progesterone reduced the risk of UEX-IF (OR = 0.306; 95% CI = 0.166, 0.567). A rapid and inexpensive method for genotyping novel LIFR gene polymorphism through T- ARMS-PCR was successfully developed. LIFR gene SNP (rs121912501) had significant association (χ2 = 200.681, P <.05) with UEX-IF. LIFR rs121912501 “TT” genotype (OR = 5.417; 95% CI = 1.868, 15.709) and “CT” genotype (OR = 3.104, 95% CI = 1.586,6.076) were at increased risk of infertility. Conclusion: UEX-IF can be caused by LIFR gene variation irrespective of increased P. It may open the doors for the discovery of new management plans for infertile women.
UR - http://www.scopus.com/inward/record.url?scp=85105929971&partnerID=8YFLogxK
U2 - 10.1111/ijcp.14245
DO - 10.1111/ijcp.14245
M3 - Article
C2 - 33914392
AN - SCOPUS:85105929971
SN - 1368-5031
VL - 75
JO - International Journal of Clinical Practice
JF - International Journal of Clinical Practice
IS - 7
M1 - e14245
ER -