TY - JOUR
T1 - GALNT2 rs4846914 SNP Is Associated with Obesity, Atherogenic Lipid Traits, and ANGPTL3 Plasma Level
AU - Qaddoumi, Mohammad
AU - Hebbar, Prashantha
AU - Abu-Farha, Mohamed
AU - Somaly, Aseelah Al
AU - Melhem, Motasem
AU - Al-Kayal, Fadi
AU - Alkhairi, Irina
AU - Cherian, Preethi
AU - Alanbaei, Muath
AU - Al-Mulla, Fahd
AU - Abubaker, Jehad
AU - Thanaraj, Thangavel Alphonse
N1 - Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/7
Y1 - 2022/7
N2 - N-Acetylgalactosaminyltransferase 2 (GALNT2) is associated with serum lipid levels, insulin resistance, and adipogenesis. Additionally, angiopoietin-like (ANGPTL) proteins have emerged as regulators of lipoprotein lipase and lipid metabolism. In this study, we evaluated the association between GALNT2 rs4846914 variant, known for its association with lipid levels in European cohorts, with plasma levels of ANGPTL proteins, apolipoproteins, lipids, and obesity traits in individuals of Arab ethnicity. GALNT2 rs4846914 was genotyped in a cohort of 278 Arab individuals from Kuwait. Plasma levels of ANGPTL3 and ANGPTL8 were measured by ELISA and apolipoproteins by Lu-minex multiplexing assay. Allele-based association tests were performed with Bonferroni-corrected p-value thresholds. The GALNT2 rs4846914_G allele was associated with increased ANGPTL3 (p-values ≤ 0.05) but not with ANGPTL8 plasma levels. The allele was associated significantly with higher BMI and weight (p-values < 0.003), increased ApoC1 levels (p-values ≤ 0.006), and reduced HDL levels (p-values ≤ 0.05). Individuals carrying the GG genotype showed significantly decreased HDL and increased BMI, WC, ApoC1, and TG. Interactions exist between (AG+GG) genotypes and measures of percentage body fat, ApoA1A, ApoC1, and ApoB48-mediated HDL levels. GALNT2 is confirmed further as a potential link connecting lipid metabolism and obesity and has the potential to be a drug target for treating obesity and dyslipidemia.
AB - N-Acetylgalactosaminyltransferase 2 (GALNT2) is associated with serum lipid levels, insulin resistance, and adipogenesis. Additionally, angiopoietin-like (ANGPTL) proteins have emerged as regulators of lipoprotein lipase and lipid metabolism. In this study, we evaluated the association between GALNT2 rs4846914 variant, known for its association with lipid levels in European cohorts, with plasma levels of ANGPTL proteins, apolipoproteins, lipids, and obesity traits in individuals of Arab ethnicity. GALNT2 rs4846914 was genotyped in a cohort of 278 Arab individuals from Kuwait. Plasma levels of ANGPTL3 and ANGPTL8 were measured by ELISA and apolipoproteins by Lu-minex multiplexing assay. Allele-based association tests were performed with Bonferroni-corrected p-value thresholds. The GALNT2 rs4846914_G allele was associated with increased ANGPTL3 (p-values ≤ 0.05) but not with ANGPTL8 plasma levels. The allele was associated significantly with higher BMI and weight (p-values < 0.003), increased ApoC1 levels (p-values ≤ 0.006), and reduced HDL levels (p-values ≤ 0.05). Individuals carrying the GG genotype showed significantly decreased HDL and increased BMI, WC, ApoC1, and TG. Interactions exist between (AG+GG) genotypes and measures of percentage body fat, ApoA1A, ApoC1, and ApoB48-mediated HDL levels. GALNT2 is confirmed further as a potential link connecting lipid metabolism and obesity and has the potential to be a drug target for treating obesity and dyslipidemia.
KW - ANGPTL3
KW - GALNT2
KW - lipid metabolism
KW - obesity
UR - http://www.scopus.com/inward/record.url?scp=85133654299&partnerID=8YFLogxK
U2 - 10.3390/genes13071201
DO - 10.3390/genes13071201
M3 - Article
C2 - 35885984
AN - SCOPUS:85133654299
SN - 2073-4425
VL - 13
JO - Genes
JF - Genes
IS - 7
M1 - 1201
ER -
