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Lipids in health and disease
Dec 19, 2019;18 (1): 224.

Sequence analysis and variant identification at the APOC3 gene locus indicates association of rs5218 with BMI in a sample of Kuwaiti's.

Zainab H Malalla, Ahmad E Al-Serri, Huda M AlAskar, Wafaa Y Al-Kandari, Suzanne A Al-Bustan
Author Information
  1. Zainab H Malalla: Department of Biological Sciences, Faculty of Science, Kuwait University, Kuwait, Kuwait.
  2. Ahmad E Al-Serri: Human Genetics Unit, Department of Pathology, Faculty of Medicine, Kuwait University, Hawally, Kuwait.
  3. Huda M AlAskar: Department of Biological Sciences, Faculty of Science, Kuwait University, Kuwait, Kuwait.
  4. Wafaa Y Al-Kandari: Department of Biological Sciences, Faculty of Science, Kuwait University, Kuwait, Kuwait.
  5. Suzanne A Al-Bustan: Department of Biological Sciences, Faculty of Science, Kuwait University, Kuwait, Kuwait. s.albustan@ku.edu.kw. ORCID
PMID: 31856839 DOI: 10.1186/s12944-019-1165-6

Abstract

BACKGROUND: APOC3 is important in lipid transport and metabolism with limited studies reporting genetic sequence variations in specific ethnic groups. The present study aimed to analyze the full APOC3 sequence among Kuwaiti Arabs and test the association of selected variants with lipid levels and BMI.
METHODS: Variants were identified by Sanger sequencing the entire APOC3 gene in 100 Kuwaiti Arabs. Variants and their genotypes were fully characterized and used to construct haplotype blocks. Four variants (rs5128, rs2854117, rs2070668, KUAPOC3N3 g.5196 A > G) were selected for testing association with serum lipid levels and BMI in a cohort (n = 733).
RESULTS: APOC3 sequence (4.3 kb) of a Kuwaiti Arab was deposited in Genbank (accession number KJ437193). Forty-two variants including 3 novels were identified including an "A" insertion at genomic positions 116,700,599-116,700,600 (promoter region) and two substitutions in intron 1 at genomic positions 116,700,819 and 116,701,159. Only three variants, (rs5128, rs2854117, and rs2070668) were analyzed for association of which rs5128 showed a trend for association with increased BMI, TG and VLDL levels that was further investigated using multivariate analysis. A significant association of rs5128 with BMI (p <  0.05) was observed following a dominant genetic model with increased risk by an OR of 4.022 (CI: 1.13-14.30).
CONCLUSION: The present study is the first to report sequence analysis of APOC3 in an Arab ethnic group. This study supports the inclusion of rs5128 as a marker for assessing genetic risk to dyslipidemia and obesity and the inclusion of the novel variant g.5196 A > G for population stratification of Arabs.

Keywords

APOC3 Arabs BMI Genetic association Lipid levels Sequence variants

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Grants

  1. n/a/College of Graduate Studies, Kuwait University
  2. YS01/12/Kuwait University

MeSH Term

Adolescent
Adult
Aged
Apolipoprotein C-III
Arabs
Body Mass Index
Female
Genetic Association Studies
Genetic Predisposition to Disease
Genotype
Humans
Lipid Metabolism
Lipoproteins, VLDL
Male
Middle Aged
Polymorphism, Single Nucleotide
Risk Factors
Triglycerides
Young Adult

Chemicals

APOC3 protein, human
Apolipoprotein C-III
Lipoproteins, VLDL
Triglycerides
Journal Article

Word Cloud

Created with Highcharts 10.0.0APOC3associationBMIvariantsrs5128sequenceArabslevelslipidgeneticstudyKuwaiti116700analysisethnicpresentselectedVariantsidentifiedgeners2854117rs2070668g5196A > G4Arabincludinggenomicpositions1increasedriskinclusionvariantSequenceBACKGROUND:importanttransportmetabolismlimitedstudiesreportingvariationsspecificgroupsaimedanalyzefullamongtestMETHODS:Sangersequencingentire100genotypesfullycharacterizedusedconstructhaplotypeblocksFourKUAPOC3N3testingserumcohortn = 733RESULTS:3 kbdepositedGenbankaccessionnumberKJ437193Forty-two3novels"A"insertion599-116600promoterregiontwosubstitutionsintron819701159threeanalyzedshowedtrendTGVLDLinvestigatedusingmultivariatesignificantp <  005observedfollowingdominantmodelOR022CI:13-1430CONCLUSION:firstreportgroupsupportsmarkerassessingdyslipidemiaobesitynovelpopulationstratificationidentificationlocusindicatesrs5218sampleKuwaiti'sGeneticLipid

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