APOB gene product is the main apolipoprotein of chylomicrons and low density lipoproteins (LDL), and is the ligand for the LDL receptor. It occurs in plasma as two main isoforms, apoB-48 and apoB-100: the former is synthesized exclusively in the gut and the latter in the liver. The intestinal and the hepatic forms of apoB are encoded by a single gene from a single, very long mRNA. The two isoforms share a common N-terminal sequence. The shorter apoB-48 protein is produced after RNA editing of the apoB-100 transcript at residue 2180 (CAA->UAA), resulting in the creation of a stop codon, and early translation termination. Mutations in this gene or its regulatory region cause hypobetalipoproteinemia, normotriglyceridemic hypobetalipoproteinemia, and hypercholesterolemia due to ligand-defective apoB, diseases affecting plasma cholesterol and apoB levels. [From RefSeq]
In an Arab patient with hypobetalipoproteinemia and absent plasma apolipoprotein B and resulting from a consanguineous marriage, Huang et al. (1989) demonstrated deletion of the entire ApoB gene exon 21 (211 basepairs coding for amino acids 1014 to 1084).
Al-Bustan et al. (2009) investigated the possible association of clinical variables and apolipoprotein (APOE, APOCI and APOB) polymorphisms with the development of myocardial infarction (MI) and coronary heart disease (CHD) in Kuwaitis. APOB genotype was determined in 143 Kuwaiti CHD patients with (n = 88) and without (n = 55) MI and in 122 controls matched for gender and age. In this study, Al-Bustan et al. (2009) determined APOB genotype by studying a polymorphic segment in the promoter region codes for a signal peptide with two common alleles, a 27- amino-acid insertion allele (I) and a 24-amino-acid deletion allele (D). A statistically significant association was found between CHD and medical history of diabetes mellitus, hypertension, high cholesterol and family history of CHD. A highly significant association was found for family history and the development of MI. No significant differences were found for allele or genotype frequencies between CHD patients and controls. Al-Bustan et al. (2009) concluded that the strong effect of family history suggests a major genetic component for the development of CHD in Kuwaitis, but this association does not appear to be related to the APO genes investigated in this study. They also suggested that the results in this study encourage future research into these and other polymorphisms and their potential association with MI and CHD in the Kuwaiti population.
Alberto et al. (1999) determined the molecular basis of familial hypercholesterolemia in 59 patients from 31 unrelated Brazilian families. All patients were screened for the Lebanese mutation, gross abnormalities of the LDLr gene, and the point mutation in the codon 3500 of the apolipoprotein B-100 gene. None of the 59 patients presented the apoB-3500 mutation, suggesting that familial defective ApoB-100 is not a major cause of inherited hypercholesterolemia in Brazil.
Frossard et al. (1995) analyzed a random sample of 101 nationals from the United Arab Emirates for the VNTR located in the 3' region of the human ApoB gene. A total of 11 alleles (33, 35, 37, 39, 41, 43, 45, 47, 49, 51, and 53 repeats) were observed in the general population. However, the 43 and 41 repeats were the most observed alleles. Frossard and colleagues suggested that the peculiar pattern of alleles in the population of the United Arab Emirates can be quite useful for DNA fingerprinting and population genetic studies (Frossard et al., 1995).
Frossard and Lestringant (1999) used a polymerase chain reaction-based assay to investigate the allele and genotype frequency distributions of the alleles of a hypervariable region located in the 3' of the human apolipoprotein B (apoB) gene. The analysis of DNA samples of 367 unrelated UAE nationals (201 males and 166 females) revealed the presence of 18 different alleles, ranging from 21 to 55 repeats, making up 51 genotypes occurring in Hardy-Weinberg proportions with a heterozygosity index of 80.9%. This observation leads to the conclusion that this marker is very informative in the Emirati population and may be very useful for UAE-specific DNA fingerprinting as well as to assess the role of the apoB gene in cardiovascular diseases. Frossard et al. (1999) investigated the associations between genetic variations of the apoB gene and clinical diagnosis of essential hypertension. They compared the distribution of the alleles of a highly polymorphic variable number of tandem repeats localized 3' to the human apoB gene, the apoB 3' hypervariable region (HVR), in a group of normotensive and a group of hypertensive individuals. DNA samples from 437 unrelated UAE nationals (215 normotensives and 222 hypertensives) were collected. The apoB 3' HVR allele and genotype status were determined using a polymerase chain reaction-based assay. In the UAE population, Frossard and colleagues (1999) found 18 alleles underlying a total of 51 genotypes. The distribution of these alleles is significantly different between normotensive and hypertensive UAE nationals. The main peak of the distributions occurred at 35 repeats among hypertensives (with a relative frequency of 25.7% versus 19.6% in normotensives) and at 37 repeats among normotensives (28.8% versus 20.3% in hypertensives). Alleles with 21, 23, 25, 49, and 55 repeats are found in hypertensives only (with a combined relative frequency of 7.6%). Frossard et al. (1999) concluded that variations of the apoB gene, or of a nearby gene, that may be in linkage disequilibrium with these alleles play a role in the development of essential hypertension in UAE nationals.