Tag Variants of LGALS-3 Containing Haplotype Block in Advanced Carotid Atherosclerosis

J Stroke Cerebrovasc Dis. 2022 Jan;31(1):106212. doi: 10.1016/j.jstrokecerebrovasdis.2021.106212. Epub 2021 Nov 20.

Abstract

Objectives: Galectin-3 affects a variety of biological processes. It is encoded by LGALS-3, located in unique haplotype block in Caucasians. Most of the studies regarding the gal-3 role in atherosclerosis are focused exclusively on protein/mRNA levels. Genetic analyses of LGALS-3 are scarce. We sought to thoroughly examine the genetic background of gal-3 and to analyze tag variants that cover more than 80% variability of the LGALS-3 containing hap-block in association with carotid plaque presence (CPP). According to Tagger server, rs4040064 G/T, rs11628437 G/A and rs7159490 C/T cover 82% (r2 > 0.8) of the genetic variance of this hap-block. Our aims were to investigate possible association of rs4040064, rs11628437 and rs7159490 haplotypes with CPP in patients with advanced carotid atherosclerosis (CA) and to analyze their possible effect on LGALS-3 mRNA expression in carotid plaques.

Materials and methods: Study group consisted of 468 patients and 296 controls. Rs4040064, rs11628437, rs7159490 and LGALS-3 mRNA expression were detected by TaqMan® technology.

Results: We have found that haplotype TAC was associated with the cerebrovascular insult (CVI) occurrence (OR = 1.68, 95% CI = 1.09-2.58, p = 0.02), compared to the referent haplotype. OR was adjusted for hypertension, age and BMI. TAC also showed higher, but not statistically significant, LGALS-3 expression in carotid plaques.

Conclusions: Our results suggest that rs4040064, rs11628437 and rs7159490 bear no association with CPP, neither they affect LGALS-3 mRNA in carotid plaques. However, we showed a significant association of haplotype TAC with the CVI occurrence in CA patients from Serbia. Replication and validation of our results are required.

Keywords: Carotid atherosclerosis; Galectin-3; LGALS-3; Tag variants; rs11628437; rs4040064; rs7159490.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Blood Proteins
  • Carotid Arteries / diagnostic imaging*
  • Carotid Artery Diseases / diagnostic imaging
  • Carotid Artery Diseases / genetics*
  • Case-Control Studies
  • Female
  • Galectin 3 / genetics*
  • Galectins
  • Genetic Predisposition to Disease
  • Haplotypes
  • Humans
  • Male
  • Middle Aged
  • Plaque, Atherosclerotic / genetics*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Serbia

Substances

  • Blood Proteins
  • Galectin 3
  • Galectins
  • LGALS3 protein, human
  • RNA, Messenger