Short tandem repeat near hypoxia response element (HRE) instead of HRE genetic variants in promoter calcitonin receptor-like receptor (CRLR) gene as risk factor in severe preeclampsia: a preliminary study

Abstract

Objective Calcitonin receptor-like receptor (CRLR) regulates vasoconstriction and dilatation; the expression increases during hypoxia via activation of hypoxia response element (HRE) in CRLR gene promoter region. Variant in HRE, as well short tandem repeat (STR) variants near HRE in CRLR alters the gene expression. This study focused on a case–control study to investigate the expression of genetic typing CLRL promoter variant in pregnant women with severe preeclampsia and normal pregnancies, we also tried to describe interesting findings of the genetic expression in anemic patients in the severe preeclampsia group. Our aimed to observe the correlation of CRLR gene promoter variant and anemia in severe preeclampsia. Results There was no nucleotide variant in HRE; CACA box prior to HRE varied in length (15–24); CACA box with length > 20 was used as cut off point. Hb was lower in CACA box length ≥ 21 (10.33 ± 1.57) vs. < 21 (11.01 ± 1.67; p = 0.391). CACA box polymorphism and anemia were correlated in severe preeclampsia (p = 0.005) OR 0.038 (CI 0.003–0.544); not in normal (p = 0.069).

Novel protein interaction network of human calcitonin receptor-like receptor revealed by label-free quantitative proteomics

“…In murine skin, total conditional knockout of Calcrl leads to developmentally arrested lymphatic capillaries, dermal lymphangiectasia, increased lymphatic permeability and prolonged oedema (Hoopes et al, 2012). The roles for CLR function in other than skin tissues, and its implication in diseases and disorders such as clear cell renal cell carcinoma (CCRCC), acute myeloid leukaemia (AML), stroke and migraine have been reported (Angenendt et al, 2019;Edvinsson et al, 2018;Gluexam et al, 2019;Herlambang et al, 2021;Koyama et al, 2017;Larrue et al, 2021;Nikitenko, Leek, et al, 2013). The use of monoclonal antibody-based drugs targeting CLR-mediated function for migraine prophylaxis, such as erenumab and galcanezumab, has been associated with impaired wound healing in skin, along with development of skin reactions and side effects such as swelling, rashes or pruritus (Bangs et al, 2020;Wurthmann et al, 2020;Göbel et al, 2022;Schenk et al, 2022).…”

Short Tandem Repeat DNA Profiling Using Perylene-Oligonucleotide Fluorescence Assay

“…This property enables one to identify a specific individual based on genotyping the STR variations. This application is the basis of widely used forensic applications, , population and disease studies, − as well as cell line profiling. − Their presence is also related to secondary DNA motifs like hairpins or G quadruplex complexes and serious pathologies such as cancer, , among others. − …”

Quantitative proteomics reveals CLR interactome in primary human cells

“…CLR is expressed and mediates essential functions in several cell types, including blood and lymphatic vessel endothelial cells (EC), vascular smooth muscle cells (VSMCs), cardiomyocytes, neurons, and cancer cells ( 10 , 11 , 12 , 13 , 14 , 15 ). CLR and its three putative peptide agonists–adrenomedullin (AM), calcitonin gene-related peptide (CGRP), and AM2/intermedin are implicated in cardiovascular and skin diseases, migraine, and cancer ( 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 ). Targeting the CLR signaling axis for migraine prophylaxis has been associated with impaired wound healing, ischemic events, and side effects ( 27 , 28 , 29 , 30 , 31 ).…”