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BMC Endocrine Disorders
Published in: BMC Endocrine Disorders 1/2020

01-12-2020 | Arterial Occlusive Disease | Research article

Putative functional non-coding polymorphisms in SELP significantly modulate sP-selectin levels, arterial stiffness and type 2 diabetes mellitus susceptibility

Authors: Raminderjit Kaur, Jatinder Singh, Rohit Kapoor, Manpreet Kaur

Published in: BMC Endocrine Disorders | Issue 1/2020

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Abstract

Background

P-selectin, encoded by SELP, has been implicated as an important molecule in the development of arterial stiffness, consequently leading to vascular complications in T2DM. SELP polymorphisms and increased levels of soluble P-selectin (sP-selectin) have been shown to be associated with several inflammatory diseases. The present work was designed to assess nine putative functional non-coding SELP variants in relation to sP-selectin levels and arterial stiffness in T2DM.

Methods

The genetic distribution of rs3917655, rs3917657, rs3917739, rs2235302, rs3917843 was determined by restriction fragment length polymorphism–polymerase chain reaction (RFLP-PCR). Genotyping of rs3917779 was performed by tetra primer amplification-refractory mutation system (ARMS)- PCR. Three SNPs i.e. rs3917853, rs3917854, rs3917855 were genotyped by Sanger sequencing. Construction of haplotypes was performed using PHASE software. The data thus obtained was analyzed by appropriate statistical tools.

Results

Two non-coding variants i.e. rs3917657 and rs3917854 of SELP were found to be associated with 2 and 1.7 -fold risk of disease development respectively. However, one non-coding variant rs2235302 was found to provide protection against disease development. Furthermore, variant allele of rs3917854 in T2DM patients was found to be associated with 2.07-fold very high vascular risk. Non-coding haplotype GCAGGCCGC was conferring 4.14-fold risk of disease development. Furthermore, overall sP-selectin levels were higher in T2DM patients when segregated according to genotypes as well as haplotypes. Significant genotype- phenotype correlation was observed for rs3917655 as well as rs3917739 variant in patients and for rs3917854 in controls. In vascular risk categories, a significant genotype- phenotype correlation was observed for rs3917655 and rs2235302. Furthermore, patients with CCGGGCCGC haplotype in high risk category were observed with higher levels of sP-selectin as compared to other haplotypes (p < 0.05).

Conclusions

Non-coding SELP variants may significantly modulate sP-selectin levels, vascular risk and T2DM susceptibility.
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Metadata
Title
Putative functional non-coding polymorphisms in SELP significantly modulate sP-selectin levels, arterial stiffness and type 2 diabetes mellitus susceptibility
Authors
Raminderjit Kaur
Jatinder Singh
Rohit Kapoor
Manpreet Kaur
Publication date
01-12-2020
Publisher
BioMed Central
Published in
BMC Endocrine Disorders / Issue 1/2020
Electronic ISSN: 1472-6823
DOI
https://doi.org/10.1186/s12902-020-00548-x

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