Key result
The GALNT2 rs4846914_G allele was significantly associated with obesity status (OR 1.45; 95% CI 1.024-2.055; P=0.036) and increased ANGPTL3 plasma levels.
Why the study?
The GALNT2 gene and its rs4846914 variant associate with lipid levels, but their relationship with plasma ANGPTL3, ANGPTL8, and apolipoproteins in Arab populations had not been evaluated.
Does the GALNT2 rs4846914 variant associate with altered plasma levels of ANGPTL proteins, apolipoproteins, and obesity in Arab individuals?
Cohort (n=278)
Does the GALNT2 rs4846914 variant associate with altered plasma levels of ANGPTL proteins, apolipoproteins, and obesity in Arab individuals?
Odds Ratio: 1.45 (95% CI 1.024–2.055)
p-value: p=0.036
The GALNT2 rs4846914_G allele is associated with increased ANGPTL3 levels, altered lipid profiles, and obesity in an Arab cohort, suggesting a genetic link to lipid metabolism.
Should not yet change clinical practice; hypothesis-generating for GALNT2-ANGPTL3 pathway in obesity.
Background: Polypeptide N-Acetylgalactosaminyltransferase 2 (GALNT2) gene has been associated with serum lipid levels, insulin resistance, and adipogenesis. One of its variants, rs4846914 has been shown to associate with Triglycerides and HDL levels in global genome-wide association studies. ANGPTL proteins have emerged as important regulators of lipid metabolism through its regulation of lipoprotein lipase activity. In this study we aimed to evaluate the association between GALNT2 variant with plasma level of ANGPTL3, 8 and apolipoproteins in individuals of Arab ethnicity. Methods: GALNT2 rs4846914 variant was genotyped in a cohort of 278 Arab individuals from Kuwait. Plasma levels of ANGPTL3 and 8 were measured by ELISA. Apolipoproteins were measured by Luminex multiplexing assay. Significance of association signals was assessed using Bonferroni-corrected P-values. Results: The GALNT2 rs4846914_G allele was associated with increased ANGPTL3 but not ANGPTL8 plasma levels. It was associated with obesity status with an odds ratio of 1.45 (CI:1.024-2.055) (P-value =0.036) . It also associated with increased levels of ApoC1 (P-values ≤0.006) and lower levels of HDL (P-values ≤0.05) . Levels of HDL were found to be mediated by interactions between genotypes (AG+GG) at rs4846914 and measures of percentage body fat (PBF) , apolipoproteins A1a, C1 and B48. Conclusions: Association between GALNT2 variant and lipid metabolism could be mediated through the increased ANGPTL3 protein level.
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THANGAVEL et al. (2022) conducted a cohort in Obesity and lipid metabolism (n=278). GALNT2 rs4846914_G allele was evaluated on obesity status (OR 1.45, 95% CI 1.024-2.055, p=0.036). The GALNT2 rs4846914_G allele was significantly associated with obesity status (OR 1.45; 95% CI 1.024-2.055; P=0.036) and increased ANGPTL3 plasma levels.
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