Identification of related long non-coding RNAs and mRNAs in subclinical hypothyroidism complicated with type 2 diabetes by transcriptome analysis — a preliminary study

Abstract

Introduction: The pathology mechanism of subclinical hypothyroidism and subclinical hypothyroidism complicated with type 2 diabetes remained uncertain. We aimed to find potential related long non-coding RNAs (lncRNAs) and mRNAs in the above diseases. Material and methods: Transcriptome sequencing was performed in three patients with subclinical hypothyroidism (S), three patients with subclinical hypothyroidism complicated with type 2 diabetes (SD), and three healthy controls (N). Differentially expressed mRNAs (DEmRNAs) and differentially expressed lncRNAs (DElncRNAs) were screened in S vs. N, SD vs. N, and SD vs. S group, and the nearby and co-expressed DEmRNAs of DElncRNAs were screened in S vs. N and SD vs. N. Moreover, functional analysis of DEmRNAs was then performed by Metascape. Results: In total, 465, 1058, and 943 DEmRNAs were obtained in S vs. N, SD vs. N, SD vs. S, respectively, and 191 overlapping genes were obtained in S vs. N and SD vs. N group. Among which, LAIR2, PNMA6A, and SFRP2 were deduced to be involved in subclinical hypothyroidism, and GPR162, APOL4, and ANK1 were deduced to be associated with subclinical hypothyroidism complicated with type 2 diabetes. A total of 50, 100, and 88 DElncRNAs were obtained in S vs. N, SD vs. N and SD vs. S, respectively. Combining with the interaction network of DElncRNA-DEmRNA, PAX8-AS1, co-expressed with KIR3DL1, was identified to function in subclinical hypothyroidism, and JHDM1D-AS1, co-expressed with ANK1, was deduced to play a role in subclinical hypothyroidism complicated with type 2 diabetes. Conclusions: Dysfunctional lncRNAs and mRNAs may be involved in the development of subclinical hypothyroidism and subclinical hypothyroidism complicated with type 2 diabetes.

Association of LncRNA-PAX8-AS1 and LAIR-2 polymorphisms along with their expression with clinical and subclinical hypothyroidism

“…Hypothyroidism is a common condition with devastating health consequences that affect about 5% of the general population. The declined thyroid hormones secretion evokes a decrease in the metabolic rate and can incur a life-threatening myxedema and other symptoms resulting in a great social and economic encumbrance 1 , 2 .…”

“…According to the degree of thyroid function reduction, clinical and subclinical hypothyroidism cases were distinguished 1 , 2 . Subclinical hypothyroidism, the earliest biochemical abnormality in hypothyroidism, is characterized by mildly elevated serum thyrotropin or thyroid stimulating hormone (TSH) levels recording > 4.5 mIU/L but < 10 mIU/L, associated with normal serum thyroxine (T4) and triiodothyronine (T3) concentrations in the absence of obvious clinical manifestations.…”

“…Importantly, several molecules were deduced to function in hypothyroidism, the lncRNA-paired-box gene 8-antisense RNA 1 (LncRNA-PAX8-AS1) and the leukocyte-associated Ig-like receptor-2 (LAIR-2) were proposed as one of the most important in such condition 1 , 13 .…”