Egyptian Drug Authority, Cairo, Egypt.
Biochemistry Department, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt.
Sci Rep. 2023 Jan 2;13(1):6. doi: 10.1038/s41598-022-26346-0.
The genetic and epigenetic architecture of clinical and subclinical hypothyroidism remains unclear. We investigated the impact of long noncoding RNA (LncRNA)-PAX8-AS1 and LAIR-2 genetic variants on the susceptibility to clinical and subclinical hypothyroidism, their influence on LncRNA-PAX8-AS1 and LAIR-2 expression and their potential as hypothyroid biomarkers. Hundred clinical hypothyroid patients, 110 subclinical hypothyroid patients, and 95 healthy controls were enrolled. Gene expression analysis and genotyping were performed by qPCR. LAIR-2 protein, a proinflammatory mediator, was tested by ELISA. Serum LncRNA-PAX8-AS1 was downregulated, whereas LAIR-2 mRNA and protein levels were upregulated in clinical and subclinical hypothyroid patients compared to healthy controls. LncRNA-PAX8-AS1 rs4848320 and rs1110839 were associated with increased risk of clinical hypothyroidism. Interestingly, both SNPs were associated with differential expression of serum LncRNA-PAX8-AS1 among clinical hypothyroid patients. LAIR-2 rs2287828 was associated with elevated risk of both clinical and subclinical hypothyroidism. Harboring the rs2287828 T allele augmented the LAIR-2 mRNA expression among clinical hypothyroid patients, while elevated both LAIR-2 mRNA and protein levels in subclinical hypothyroid patients. The rs4848320-rs1110839-rs2287828 TTT, CTT, and CGT haplotypes were associated with increased hypothyroid risk. Surprisingly, serum LncRNA-PAX8-AS1 and LAIR-2 mRNA expression demonstrated superior diagnostic accuracy for clinical hypothyroidism and turned out as independent predictors in the multivariate analysis. Conclusively, LncRNA-PAX8-AS1 and LAIR-2 genetic variants are novel genetic biomarkers of hypothyroidism that could alter the LncRNA-PAX8-AS1 and LAIR-2 expression. LncRNA-PAX8-AS1 and LAIR-2 expression profiles have the potential as effective diagnostic and prognostic indicators of hypothyroidism.
临床和亚临床甲状腺功能减退的遗传和表观遗传结构仍不清楚。我们研究了长非编码 RNA（LncRNA）-PAX8-AS1 和 LAIR-2 遗传变异对临床和亚临床甲状腺功能减退易感性的影响，它们对 LncRNA-PAX8-AS1 和 LAIR-2 表达的影响，以及它们作为甲状腺功能减退生物标志物的潜力。招募了 100 名临床甲状腺功能减退患者、110 名亚临床甲状腺功能减退患者和 95 名健康对照者。通过 qPCR 进行基因表达分析和基因分型。通过 ELISA 测试促炎介质 LAIR-2 蛋白。与健康对照组相比，临床和亚临床甲状腺功能减退患者的血清 LncRNA-PAX8-AS1 下调，而 LAIR-2 mRNA 和蛋白水平上调。LncRNA-PAX8-AS1 rs4848320 和 rs1110839 与临床甲状腺功能减退的风险增加相关。有趣的是，这两个 SNP 与临床甲状腺功能减退患者血清 LncRNA-PAX8-AS1 的差异表达有关。LAIR-2 rs2287828 与临床和亚临床甲状腺功能减退的风险增加相关。携带 rs2287828 T 等位基因会增加临床甲状腺功能减退患者的 LAIR-2 mRNA 表达，而在亚临床甲状腺功能减退患者中则会同时增加 LAIR-2 mRNA 和蛋白水平。rs4848320-rs1110839-rs2287828 TTT、CTT 和 CGT 单倍型与甲状腺功能减退风险增加相关。令人惊讶的是，血清 LncRNA-PAX8-AS1 和 LAIR-2 mRNA 表达对临床甲状腺功能减退具有更高的诊断准确性，并在多变量分析中成为独立预测因子。总之，LncRNA-PAX8-AS1 和 LAIR-2 遗传变异是甲状腺功能减退的新型遗传生物标志物，可改变 LncRNA-PAX8-AS1 和 LAIR-2 的表达。LncRNA-PAX8-AS1 和 LAIR-2 的表达谱具有作为甲状腺功能减退有效诊断和预后指标的潜力。
