了解TNFα - 308多态性在复发性流产发病机制中的潜在免疫遗传学作用。
Understanding the potential immunogenetic role of TNFα-308 polymorphism in the pathogenesis of recurrent miscarriage.
作者信息
Ali Shafat, Majid Sabhiya, Ali Md Niamat, Banday Mujeeb Zafar, Taing Shahnaz
机构信息
Cytogenetics and Molecular Biology Laboratory, Centre of Research for Development, University of Kashmir, Jammu and Kashmir, Srinagar, 190006, India.
Department of Biochemistry, Government Medical College, Jammu and Kashmir, Srinagar, 190010, India.
出版信息
Heliyon. 2023 Apr 3;9(4):e15166. doi: 10.1016/j.heliyon.2023.e15166. eCollection 2023 Apr.
BACKGROUND
Recurrent miscarriage (RM) represents the spontaneous termination of two or more successive pregnancies. TNFα is a proinflammatory cytokine that is often considered harmful for embryonic development when expressed beyond normal levels.
AIM
The study was conducted to assess the association between TNFα-308 polymorphism and RM pathogenesis.
METHODS
Samples of blood were obtained from patients and controls through venipuncture. The levels of TNFα in serum were measured by ELISA. TNFα gene promoter-associated single-nucleotide polymorphism was investigated with polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) techniques with precise primers and the restriction endonuclease, NcoI.
RESULTS
Serum TNFα levels in patients were considerably high (p < 0.05) than controls. The genotype and allele frequencies for TNFα gene polymorphism differs significantly (p = 0.0089; p = 0.0043 respectively) between patients and controls. The TNFα-308 SNP exhibited a link with higher RM risk in heterozygous (GG vs. GA; OR: 3.086, 95% CI: 1.475-6.480; p: ), dominant (GG vs. GA + AA; OR: 2.919, 95% CI: 1.410-6.056, p: ), and allelic/codominant (G vs. A; OR: 2.449, 95% CI: 1.313-4.644, p: ) models. However, this SNP showed an insignificant association with higher and lower RM risk in homozygous (GG vs. AA; OR: 1.915, 95% CI: 0.3804-10.99, p: 0.6560) and recessive (AA vs. GA + GG; OR: 0.6596, 95% CI: 0.1152-3.297, p: >0.9999) models, respectively. Further, the TNFα-308G/A genotype frequencies were in concord with HWE both in the controls (χ = 3.235; p = 0.1985) and the patients (χ = 0.0117; p = 0.9942).
CONCLUSION
The serum TNFα levels were significantly higher in the patients than the controls. The genotyping analysis also demonstrated that TNFα-308G/A SNP significantly increases the overall risk of RM, suggesting that the SNP modulates the TNFα gene expression and thereby increases serum TNFα levels that adversely affect the pregnancy outcome.
背景
复发性流产（RM）是指连续两次或更多次自然终止妊娠。肿瘤坏死因子α（TNFα）是一种促炎细胞因子，当其表达超过正常水平时，通常被认为对胚胎发育有害。
目的
本研究旨在评估TNFα - 308多态性与RM发病机制之间的关联。
方法
通过静脉穿刺从患者和对照组获取血样。采用酶联免疫吸附测定法（ELISA）检测血清中TNFα的水平。使用精确引物和限制性内切酶NcoI，通过聚合酶链反应（PCR）和限制性片段长度多态性（RFLP）技术研究TNFα基因启动子相关的单核苷酸多态性。
结果
患者血清TNFα水平显著高于对照组（p < 0.05）。患者和对照组之间TNFα基因多态性的基因型和等位基因频率存在显著差异（分别为p = 0.0089；p = 0.0043）。在杂合子（GG与GA；比值比：3.086，95%置信区间：1.475 - 6.480；p：）、显性（GG与GA + AA；比值比：2.919，95%置信区间：1.410 - 6.056，p：）和等位基因/共显性（G与A；比值比：2.449，95%置信区间：1.313 - 4.644，p：）模型中，TNFα - 308单核苷酸多态性（SNP）与较高的RM风险相关。然而，在纯合子（GG与AA；比值比：1.915，95%置信区间：0.3804 - 10.99，p：0.6560）和隐性（AA与GA + GG；比值比：0.6596，95%置信区间：0.1152 - 3.297，p：>0.9999）模型中，该SNP与较高和较低的RM风险之间的关联不显著。此外，TNFα - 308G/A基因型频率在对照组（χ = 3.235；p = 0.1985）和患者组（χ = 0.0117；p = 0.9942）中均符合哈迪 - 温伯格平衡（HWE）。
结论
患者血清TNFα水平显著高于对照组。基因分型分析还表明，TNFα - 308G/A SNP显著增加了RM的总体风险，表明该SNP调节TNFα基因表达，从而增加血清TNFα水平，对妊娠结局产生不利影响。
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