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Gene & Protein in Disease rs670 SNP in APOA1 gene

the liver and small intestine, is present in very low-density 2. Methods
lipoprotein (VLDL) and high-density lipoprotein (HDL).
It is the primary protein component of HDL, acting This integrative review comprehensively analyzed studies
as a ligand for scavenger receptor B Type 1 (SR-B1) in on the rs670 polymorphism of APOA1 available up to
hepatocytes and macrophages and as a cofactor for lecithin July 2024. The databases used were as follows: database
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cholesterol acyltransferase. Genetic alterations in APOA1 of single-nucleotide polymorphisms (dbSNP; www.ncbi.
are associated with lipid metabolism disorders, particularly nlm.nih.gov/snp/), 14 LitVar2 (www.ncbi.nlm.nih.gov/
hypoalphalipoproteinemia, hypertriglyceridemia, and research/litvar2/), Scopus (www.scopus.com/), and
familial systemic amyloidosis. 2 ScienceDirect (www.sciencedirect.com/). Searches in
the Scopus and ScienceDirect databases were performed
APOA1 spans 2,200 bases and is located on using the following search string: [“rs670” OR “−75GA”
chromosome 11q23.3. Its transcription yields four exons AND “APOA-I” OR “APOA1”]. The dbSNP and LitVar2
that are processed during splicing to code for pre-pro- databases, which index PubMed articles, provided a
Apo A-I, a protein with 267 amino acid residues. Within curated list of articles related to the rs670 polymorphism.
the cell, 18 NH -terminal residues are cleaved to form
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Pro-Apo A-I (249 residues), which is then secreted into The inclusion criteria applied to the searches were as
the plasma. Subsequently, six additional NH -terminal follows: (1) full-text articles to allow for critical analysis
2
residues are removed to produce mature Apo A-I, and (2) articles including either minor allele frequency
comprising 243 amino acid residues. APOA1 is part (MAF) or a contingency table with genotype distributions.
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of the APO cluster on chromosome 11, which encodes Review articles, meta-analyses, genome-wide association
Apo A-I, Apo C-III, Apo A-IV, and Apo A-V. This cluster studies (GWASs), and duplicate articles were excluded.
underscores the relevance of genetic alterations in Eligible studies were selected regardless of their publication
influencing lipid metabolism. 4 language or year.
In 1984, a cytosine–phosphate–guanine (CpG) site 3. Results
in the APOA1 promoter region was identified as a “hot Of the 162 articles retrieved during the searches, 21 were
spot” for polymorphisms using the MspI restriction not available in full text, 36 were review articles and/or
enzyme. Due to the high methylation rate of CpG meta-analyses, 12 were GWAS, and 24 did not report MAF
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sites in promoter regions, a cytosine (C) to thymine (T) or genotype distributions. After applying the inclusion
transition, likely caused by the spontaneous deamination criteria, 69 articles remained, and following the removal
of 5-methylcytosine, resulted in the SNP rs670 (C>T) of duplicates, 28 articles were selected for data collection.
at position 75 upstream of the gene start region. Over The extracted data included study type, year of publication,
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time, the exact position of this polymorphism has been research location, population sample size, allelic and
described using various denominations. Initially reported genotypic frequencies, and conclusions regarding the
as a guanine (G) to adenine (A) substitution in the
DNA template strand at positions −78 (−78G > A), −76 rs670 polymorphism. A flowchart illustrating the selection
(−76G > A), and −75 (−75G > A), it was later defined as process is provided in Figure 1, whereas the key findings
6-8
are summarized in Table 1.
a −75G > A substitution on the template strand and rs670
(C>T) on the coding strand. 9 The 28 articles selected for data collection were
published between 2009 and 2023, and they comprised
Structural and expression changes in Apo A-I caused
by genetic polymorphisms have been linked to lipid 14 (50.0%) case–control studies, 10 (35.72%) cross-
metabolism disorders. The rs670 SNP was initially sectional studies, 2 (7.14%) cohort studies, and 2 (7.14%)
2
associated with altered Apo A-I expression and HDL clinical trials. Geographically, the studies were distributed
cholesterol (HDL-c) levels. Over time, its associations across Asia (15 studies; 53.57%), America (8 studies;
28.57%), Europe (4 studies; 14.29%), and Africa (1 study;
with various metabolic disorders, cardiovascular diseases, 3.57%), as illustrated in Figure 2.
neurodegenerative diseases, and cancers have been
studied. 6,7,10-13 Given the importance of understanding Regarding the clinical associations of the rs670
how SNPs interact with environmental factors and polymorphism, 14 studies (50.0%) focused on lipid
their potential impact on population health, this review metabolism disorders. Six studies found no association
aimed to compile and describe key findings related to between the polymorphism and metabolic syndromes,
the rs670 SNP, with special emphasis on its potential role including obesity, dyslipidemia, hyperglycemia, and
in regulating gene expression within the APO cluster on hypertension. However, eight studies reported significant
chromosome 11. associations with metabolic syndromes (odds ratio

Volume 4 Issue 1 (2025) 2 doi: 10.36922/gpd.4354