<i>GALNT2</i> rs4846914 SNP Is Associated with Obesity, Atherogenic Lipid Traits, and ANGPTL3 Plasma Level
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 <i...
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| Format: | Article |
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MDPI AG
2022-07-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/13/7/1201 |
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| author | Mohammad Qaddoumi Prashantha Hebbar Mohamed Abu-Farha Aseelah Al Somaly Motasem Melhem Fadi Al-Kayal Irina AlKhairi Preethi Cherian Muath Alanbaei Fahd Al-Mulla Jehad Abubaker Thangavel Alphonse Thanaraj |
| author_facet | Mohammad Qaddoumi Prashantha Hebbar Mohamed Abu-Farha Aseelah Al Somaly Motasem Melhem Fadi Al-Kayal Irina AlKhairi Preethi Cherian Muath Alanbaei Fahd Al-Mulla Jehad Abubaker Thangavel Alphonse Thanaraj |
| author_sort | Mohammad Qaddoumi |
| collection | DOAJ |
| description | 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 <i>GALNT2</i> 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. <i>GALNT2</i> 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 Luminex multiplexing assay. Allele-based association tests were performed with Bonferroni-corrected <i>p</i>-value thresholds. The <i>GALNT2</i> rs4846914_G allele was associated with increased ANGPTL3 (<i>p</i>-values ≤ 0.05) but not with ANGPTL8 plasma levels. The allele was associated significantly with higher BMI and weight (<i>p</i>-values < 0.003), increased ApoC1 levels (<i>p</i>-values ≤ 0.006), and reduced HDL levels (<i>p</i>-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. |
| first_indexed | 2024-03-09T03:24:02Z |
| format | Article |
| id | doaj.art-f26ad292bed3438a958c06dc3a3874e6 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-09T03:24:02Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-f26ad292bed3438a958c06dc3a3874e62023-12-03T15:06:00ZengMDPI AGGenes2073-44252022-07-01137120110.3390/genes13071201<i>GALNT2</i> rs4846914 SNP Is Associated with Obesity, Atherogenic Lipid Traits, and ANGPTL3 Plasma LevelMohammad Qaddoumi0Prashantha Hebbar1Mohamed Abu-Farha2Aseelah Al Somaly3Motasem Melhem4Fadi Al-Kayal5Irina AlKhairi6Preethi Cherian7Muath Alanbaei8Fahd Al-Mulla9Jehad Abubaker10Thangavel Alphonse Thanaraj11Pharmacology and Therapeutics Department, Faculty of Pharmacy, Kuwait University, Kuwait City 13110, KuwaitDepartment of Genetics and Bioinformatics, Dasman Diabetes Institute, Dasman 15462, KuwaitDepartment of Biochemistry and Molecular Biology, Dasman Diabetes Institute, Dasman 15462, KuwaitPharmacology and Therapeutics Department, Faculty of Pharmacy, Kuwait University, Kuwait City 13110, KuwaitSpecial Services Facility, Dasman Diabetes Institute, Dasman 15462, KuwaitAdvanced Genomic Technologies Laboratory, McGill University, Montreal, QC H3A 0G4, CanadaDepartment of Biochemistry and Molecular Biology, Dasman Diabetes Institute, Dasman 15462, KuwaitDepartment of Biochemistry and Molecular Biology, Dasman Diabetes Institute, Dasman 15462, KuwaitDepartment of Medicine, Faculty of Medicine, Kuwait University, Kuwait City 13110, KuwaitResearch Division, Dasman Diabetes Institute, Dasman 15462, KuwaitDepartment of Biochemistry and Molecular Biology, Dasman Diabetes Institute, Dasman 15462, KuwaitDepartment of Genetics and Bioinformatics, Dasman Diabetes Institute, Dasman 15462, KuwaitN-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 <i>GALNT2</i> 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. <i>GALNT2</i> 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 Luminex multiplexing assay. Allele-based association tests were performed with Bonferroni-corrected <i>p</i>-value thresholds. The <i>GALNT2</i> rs4846914_G allele was associated with increased ANGPTL3 (<i>p</i>-values ≤ 0.05) but not with ANGPTL8 plasma levels. The allele was associated significantly with higher BMI and weight (<i>p</i>-values < 0.003), increased ApoC1 levels (<i>p</i>-values ≤ 0.006), and reduced HDL levels (<i>p</i>-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.https://www.mdpi.com/2073-4425/13/7/1201GALNT2ANGPTL3obesitylipid metabolism |
| spellingShingle | Mohammad Qaddoumi Prashantha Hebbar Mohamed Abu-Farha Aseelah Al Somaly Motasem Melhem Fadi Al-Kayal Irina AlKhairi Preethi Cherian Muath Alanbaei Fahd Al-Mulla Jehad Abubaker Thangavel Alphonse Thanaraj <i>GALNT2</i> rs4846914 SNP Is Associated with Obesity, Atherogenic Lipid Traits, and ANGPTL3 Plasma Level Genes GALNT2 ANGPTL3 obesity lipid metabolism |
| title | <i>GALNT2</i> rs4846914 SNP Is Associated with Obesity, Atherogenic Lipid Traits, and ANGPTL3 Plasma Level |
| title_full | <i>GALNT2</i> rs4846914 SNP Is Associated with Obesity, Atherogenic Lipid Traits, and ANGPTL3 Plasma Level |
| title_fullStr | <i>GALNT2</i> rs4846914 SNP Is Associated with Obesity, Atherogenic Lipid Traits, and ANGPTL3 Plasma Level |
| title_full_unstemmed | <i>GALNT2</i> rs4846914 SNP Is Associated with Obesity, Atherogenic Lipid Traits, and ANGPTL3 Plasma Level |
| title_short | <i>GALNT2</i> rs4846914 SNP Is Associated with Obesity, Atherogenic Lipid Traits, and ANGPTL3 Plasma Level |
| title_sort | i galnt2 i rs4846914 snp is associated with obesity atherogenic lipid traits and angptl3 plasma level |
| topic | GALNT2 ANGPTL3 obesity lipid metabolism |
| url | https://www.mdpi.com/2073-4425/13/7/1201 |
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