Sequence Analysis of APOA5 Among the Kuwaiti Population Identifies Association of rs2072560, rs2266788, and rs662799 With TG and VLDL Levels

Abstract

Common variants of Apolipoprotein A5 (APOA5) 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 APOA5 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 APOA5 and multiple sequence alignment was used to identify variants. The complete APOA5 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 APOA5 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.

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

“…In our population we were able to replicate several associations with different lipemic traits previously reported in other ethnicities. For example, variants in the gene cluster APOA1/C3/A4/A5-ZPR1-BUD13 , such as the regulatory SNVs rs5128 in APOC3 , and rs651821 in APOA5 , as well as the missense SNV rs2072560 also within APOA5 , and the intronic variant rs2070665 in APOA1 , were all associated with HTG in our population, as they are in European, Asian, and African populations ( Feng et al, 2016 ; Fu et al, 2015 ; Jasim et al, 2018 ; Ken-Dror et al, 2010 ; Song et al, 2015 ; Zhou et al, 2013 ). Likewise, the association of the missense SNV rs1367117 in APOB with HTC has also been reported in populations of European ancestry ( Lu et al, 2010 ), whereas the association of the missense SNVs rs10488698 in BUD13 and rs9282541 in ABCA1 with low HDL-C has also been observed in Asian and Latino American populations, respectively ( Zhang et al, 2017 ; Acuña-Alonso et al, 2010 ).…”

A Clinical Case of a Homozygous Deletion in the APOA5 Gene with Severe Hypertriglyceridemia

“…HTG, caused by pathogenic variants in the APOA5 gene, is described in OMIM (145750) and HGMD as an autosomal dominant disorder. At the same time, according to ClinVar, only 18 pathogenic/probably pathogenic variants are described in this gene, while according to HGMD, there are 82 variants, and most of them are associated with an increased risk of myocardial infarction and cardiovascular diseases [ 34 , 35 , 36 ].…”

Polymorphism rs10105606 of LPL as a Novel Risk Factor for Microalbuminuria

“…The functions of rs13702, rs2266788, and rs17231506 were 3 Prime UTR Variant of LPL, APOA5, and Upstream Variant of CETP. [12][13][14] LPL was the first and second closest gene to rs10105606 and Affx-31885823. 15 APOA5 acted as the same closest gene to rs2075290, rs603446, rs3741298, and Affx-4282911, which were functioned as Intron Variant of ZPR1.…”