Sequence Analysis of Among the Kuwaiti Population Identifies Association of Rs2072560, Rs2266788, and Rs662799 With TG and VLDL Levels

Overview

Journal Front Genet

Date 2018 Apr 25

PMID 29686695

Citations 9

Authors

Anfal A Jasim

Suzanne A Al-Bustan

Wafa Al-Kandari

Ahmad Al-Serri

Huda Alaskar

Affiliations

Soon will be listed here.

Abstract

Common variants of Apolipoprotein A5 (5) have been associated with lipid levels yet very few studies have reported full sequence data from various ethnic groups. The purpose of this study was to analyse the full gene sequence to identify variants in 100 healthy Kuwaitis of Arab ethnicities and assess their association with variation in lipid levels in a cohort of 733 samples. Sanger method was used in the direct sequencing of the full 3.7 Kb and multiple sequence alignment was used to identify variants. The complete sequence in Kuwaiti Arabs has been deposited in GenBank (KJ401315). A total of 20 reported single nucleotide polymorphisms (SNPs) were identified. Two novel SNPs were also identified: a synonymous 2197G>A polymorphism at genomic position 116661525 and a 3' UTR 3222 C>T polymorphism at genomic position 116660500 based on human genome assembly GRCh37/hg:19. Five SNPs along with the two novel SNPs were selected for validation in the cohort. Association of those SNPs with lipid levels was tested and minor alleles of three SNPs (rs2072560, rs2266788, and rs662799) were found significantly associated with TG and VLDL levels. This is the first study to report the full sequence and SNPs in an Arab ethnic group. Analysis of the variants identified and comparison to other populations suggests a distinctive genetic component in Arabs. The positive association observed for rs2072560 and rs2266788 with TG and VLDL levels confirms their role in lipid metabolism.

Citing Articles

Consumption of dietary fiber and APOA5 genetic variants in metabolic syndrome: baseline data from the Korean Medicine Daejeon Citizen Cohort Study.

Kim J, Baek Y, Lee S Nutr Metab (Lond). 2024; 21(1):19.

PMID: 38581036 PMC: 10998362. DOI: 10.1186/s12986-024-00793-0.

Sequence Variant Analysis of the Locus among an Arab Cohort.

Al-Bustan S, Alrashid M, Al-Serri A, Annice B, Bahbahani H Int J Mol Sci. 2023; 24(22).

PMID: 38003484 PMC: 10671382. DOI: 10.3390/ijms242216293.

Regularized Machine Learning Models for Prediction of Metabolic Syndrome Using and Gene Variants: Tehran Cardiometabolic Genetic Study.

Alipour N, Kazemnejad A, Akbarzadeh M, Eskandari F, Zahedi A, Daneshpour M Cell J. 2023; 25(8):536-545.

PMID: 37641415 PMC: 10542204. DOI: 10.22074/cellj.2023.2000864.1294.

A Clinical Case of a Homozygous Deletion in the Gene with Severe Hypertriglyceridemia.

Vasiluev P, Ivanova O, Semenova N, Strokova T, Taran N, Chubykina U Genes (Basel). 2022; 13(6).

PMID: 35741823 PMC: 9222921. DOI: 10.3390/genes13061062.

Exome Sequencing Data Analysis and a Case-Control Study in Mexican Population Reveals Lipid Trait Associations of New and Known Genetic Variants in Dyslipidemia-Associated Loci.

Jurado-Camacho P, Cid-Soto M, Barajas-Olmos F, Garcia-Ortiz H, Baca-Peynado P, Martinez-Hernandez A Front Genet. 2022; 13:807381.

PMID: 35669185 PMC: 9164108. DOI: 10.3389/fgene.2022.807381.

References

Ouatou S, Ajjemami M, Charoute H, Sefri H, Ghalim N, Rhaissi H . Association of APOA5 rs662799 and rs3135506 polymorphisms with arterial hypertension in Moroccan patients. Lipids Health Dis. 2014; 13:60. PMC: 3972990. DOI: 10.1186/1476-511X-13-60. View

Zubair N, Graff M, Ambite J, Bush W, Kichaev G, Lu Y . Fine-mapping of lipid regions in global populations discovers ethnic-specific signals and refines previously identified lipid loci. Hum Mol Genet. 2017; 25(24):5500-5512. PMC: 5721937. DOI: 10.1093/hmg/ddw358. View

Excoffier L, Ray N . Surfing during population expansions promotes genetic revolutions and structuration. Trends Ecol Evol. 2008; 23(7):347-51. DOI: 10.1016/j.tree.2008.04.004. View

Auton A, Brooks L, Durbin R, Garrison E, Kang H, Korbel J . A global reference for human genetic variation. Nature. 2015; 526(7571):68-74. PMC: 4750478. DOI: 10.1038/nature15393. View

Schaap F, Rensen P, Voshol P, Vrins C, van der Vliet H, Chamuleau R . ApoAV reduces plasma triglycerides by inhibiting very low density lipoprotein-triglyceride (VLDL-TG) production and stimulating lipoprotein lipase-mediated VLDL-TG hydrolysis. J Biol Chem. 2004; 279(27):27941-7. DOI: 10.1074/jbc.M403240200. View

Endo K, Yanagi H, Araki J, Hirano C, Yamakawa-Kobayashi K, Tomura S . Association found between the promoter region polymorphism in the apolipoprotein A-V gene and the serum triglyceride level in Japanese schoolchildren. Hum Genet. 2002; 111(6):570-2. DOI: 10.1007/s00439-002-0825-0. View

Forte T, Shu X, Ryan R . The ins (cell) and outs (plasma) of apolipoprotein A-V. J Lipid Res. 2008; 50 Suppl:S150-5. PMC: 2674726. DOI: 10.1194/jlr.R800050-JLR200. View

Liu H, Zhang S, Lin J, Li H, Huang A, Xiao C . Association between DNA variant sites in the apolipoprotein A5 gene and coronary heart disease in Chinese. Metabolism. 2005; 54(5):568-72. DOI: 10.1016/j.metabol.2004.11.009. View

Lai C, Tai E, Tan C, Cutter J, Chew S, Zhu Y . The APOA5 locus is a strong determinant of plasma triglyceride concentrations across ethnic groups in Singapore. J Lipid Res. 2003; 44(12):2365-73. DOI: 10.1194/jlr.M300251-JLR200. View

10.

Li Y, Yin R, Lai C, Li M, Long X, Li K . Association of apolipoprotein A5 gene polymorphisms and serum lipid levels. Nutr Metab Cardiovasc Dis. 2010; 21(12):947-56. DOI: 10.1016/j.numecd.2010.04.004. View

11.

Yin R, Li Y, Lai C . Apolipoprotein A1/C3/A5 haplotypes and serum lipid levels. Lipids Health Dis. 2011; 10:140. PMC: 3170230. DOI: 10.1186/1476-511X-10-140. View

12.

Pullinger C, Aouizerat B, Movsesyan I, Durlach V, Sijbrands E, Nakajima K . An apolipoprotein A-V gene SNP is associated with marked hypertriglyceridemia among Asian-American patients. J Lipid Res. 2008; 49(8):1846-54. PMC: 2444008. DOI: 10.1194/jlr.P800011-JLR200. View

13.

Shahid S, Shabana N, Cooper J, Rehman A, Humphries S . Common variants in the genes of triglyceride and HDL-C metabolism lack association with coronary artery disease in the Pakistani subjects. Lipids Health Dis. 2017; 16(1):24. PMC: 5282842. DOI: 10.1186/s12944-017-0419-4. View

14.

Merkel M, Loeffler B, Kluger M, Fabig N, Geppert G, Pennacchio L . Apolipoprotein AV accelerates plasma hydrolysis of triglyceride-rich lipoproteins by interaction with proteoglycan-bound lipoprotein lipase. J Biol Chem. 2005; 280(22):21553-60. DOI: 10.1074/jbc.M411412200. View

15.

Li S, Hu B, Wang Y, Wu D, Jin L, Wang X . Influences of APOA5 variants on plasma triglyceride levels in Uyghur population. PLoS One. 2014; 9(10):e110258. PMC: 4196964. DOI: 10.1371/journal.pone.0110258. View

16.

Miller S, Dykes D, Polesky H . A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988; 16(3):1215. PMC: 334765. DOI: 10.1093/nar/16.3.1215. View

17.

Talmud P . Rare APOA5 mutations--clinical consequences, metabolic and functional effects: an ENID review. Atherosclerosis. 2007; 194(2):287-92. DOI: 10.1016/j.atherosclerosis.2006.12.010. View

18.

Priore Oliva C, Tarugi P, Calandra S, Pisciotta L, Bellocchio A, Bertolini S . A novel sequence variant in APOA5 gene found in patients with severe hypertriglyceridemia. Atherosclerosis. 2006; 188(1):215-7. DOI: 10.1016/j.atherosclerosis.2006.04.010. View

19.

Alwan A, King H . Diabetes in the Eastern Mediterranean (Middle East) region: the World Health Organization responds to a major public health challenge. Diabet Med. 1995; 12(12):1057-8. DOI: 10.1111/j.1464-5491.1995.tb00421.x. View

20.

Lai C, Demissie S, Cupples L, Zhu Y, Adiconis X, Parnell L . Influence of the APOA5 locus on plasma triglyceride, lipoprotein subclasses, and CVD risk in the Framingham Heart Study. J Lipid Res. 2004; 45(11):2096-105. DOI: 10.1194/jlr.M400192-JLR200. View