Background: A number of human inflammatory diseases and tumors have
been shown to cause alterations in the glycosylation pattern of plasma proteins in a specific
manner. These highly variable and versatile post-translational modifications finetune
protein functions by influencing sorting, folding, enzyme activity and subcellular
localization. However, relatively little is known about regulatory factors of this procedure
and about the accurate causative connection between glycosylation and disease.
Objective: The aim of the present study was to investigate whether certain single nucleotide
polymorphisms (SNPs) in genes encoding glycosyltransferases and glycosidases
could be associated with elevated risk for chronic obstructive pulmonary disease
(COPD) and lung adenocarcinoma.
Methods: A total of 32 SNPs localized in genes related to N-glycosylation were selected
for the association analysis. Polymorphisms with putative biological functions (missense
or regulatory variants) were recruited. SNPs were genotyped by a TaqMan OpenArray
platform. A single base extension-based method in combination with capillary gel electrophoresis
was used for verification.
Results: The TaqMan OpenArray approach provided accurate and reliable genotype
data (global call rate: 94.9%, accuracy: 99.6%). No significant discrepancy was detected
between the obtained and expected genotype frequency values (Hardy–Weinberg equilibrium)
in the healthy control sample group in case of any SNP confirming reliable sampling
and genotyping. Allele frequencies of the rs3944508 polymorphism localized in the
3’ UTR of the MGAT5 gene significantly differed between the sample groups compared.
Conclusion: Our results suggest that the rs34944508 SNP might modulate the risk for
lung cancer by influencing the expression of MGAT5. This enzyme catalyzes the addition
of N-acetylglucosamine (GlcNAc) in beta 1-6 linkage to the alpha-linked mannose of
biantennary N-linked oligosaccharides, thus, increasing branching that is the characteristic
of invasive malignancies.