Department of Physiology, Karachi Institute of Medical Sciences (KIMS), CMH, Malir Cantt., Karachi, Pakistan.
Department of Physiology, University of Karachi, Karachi, Pakistan.
Nucleosides Nucleotides Nucleic Acids. 2023;42(9):718-730. doi: 10.1080/15257770.2023.2188911. Epub 2023 Mar 16.
To explore the association of leukemia inhibitory factor receptor (LIFR) gene variant rs3099124, ovarian steroids, and leukemia inhibitory factor with unexplained infertility in Pakistani females.
A case-control investigation in which eighty-one (81) females with unexplained infertility and one hundred and sixty-two (162) fertile counterparts (age and body mass index compared) were recruited between October 2016 and 2018. Ten milliliters of venous blood was collected from all participants. "Genomic DNA" was taken out from lymphocytes in peripheral blood samples. "Tetra Amplification Refractory Mutation System Polymerase Chain Reaction (T-ARMS-PCR)" was constructed through software "Primer-I". Amplification was carried out by "T-ARMS-PCR" followed by subsequent sequencing for confirmation and extensive consonance. Estradiol, Progesterone and Leukemia Inhibitory Factor (LIF) were measured in serum by ELISA.
Statistically significant difference was noticed in genotype frequency in "LIFR-gene variant; rs3099124" (χ = 28.222, value < 0.01) between research participants. Although, rs "3099124" "AA" (OR = 0.000; 95%CI = 0-0) and "GA" genotypes (OR = 0.525; 95%CI = 0.226-1.22) showed non-significant safety/protection against unexplained infertility yet minor/risk allele "A" frequency was greater in women with unexplained infertility suggesting a possible explanation of implantation failure. LIF concentration varied between fertile and infertile groups (χ = 9.857, < 0.05) revealing significant threat of unexplained infertility in women with decreased LIF concentration (OR = 2.316, 95%CI = 1.214-4.416). Progesterone was significantly related to unexplained infertility in both study groups (χ = 20.347, < 0.05). High progesterone reduced the possibility of unexplained infertility (OR = 0.306; 95% CI = 0.166-0.567).
LIFR gene variation (rs3099124) and reduced LIF secretion may cause implantation failure in women with unexplained infertility.
探讨白血病抑制因子受体（LIFR）基因变异 rs3099124、卵巢类固醇和白血病抑制因子与巴基斯坦女性不明原因不孕的关系。
本研究采用病例对照研究，于 2016 年 10 月至 2018 年期间招募了 81 名不明原因不孕女性和 162 名健康对照组（年龄和体重指数相匹配）。所有参与者均采集 10 毫升静脉血。从外周血样本中的淋巴细胞中提取“基因组 DNA”。通过软件“Primer-I”构建“四扩增难治性突变系统聚合酶链反应（T-ARMS-PCR）”。通过“T-ARMS-PCR”进行扩增，随后进行测序以确认和广泛一致性。通过 ELISA 法测量血清中的雌二醇、孕酮和白血病抑制因子（LIF）。
研究参与者的“LIFR 基因变异；rs3099124”基因型频率存在统计学显著差异（χ = 28.222， 值<0.01）。尽管 rs“3099124”“AA”（OR = 0.000；95%CI = 0-0）和“GA”基因型（OR = 0.525；95%CI = 0.226-1.22）显示对不明原因不孕无显著安全性/保护作用，但不孕女性中较小/风险等位基因“A”的频率更高，这可能解释了着床失败。LIF 浓度在健康组和不孕组之间存在差异（χ = 9.857， < 0.05），表明 LIF 浓度降低的女性发生不明原因不孕的风险较高（OR = 2.316，95%CI = 1.214-4.416）。孕激素在两组研究中均与不明原因不孕有关（χ = 20.347， < 0.05）。高孕激素降低了不明原因不孕的可能性（OR = 0.306；95%CI = 0.166-0.567）。
LIFR 基因变异（rs3099124）和 LIF 分泌减少可能导致不明原因不孕女性着床失败。
