Common Dna Polymorphism Within Coding Sequence of Apolipoprotein B Gene Associated With Altered Lipid Levels

Law, Adam; Powell, Lynn M.; Brunt, H.; Knott, T J; Altman, D G; Rajput, Tausif Ahmed; Wallis, S.; Pease, Richard J.; Priestley, L.; Scott, James; Miller, George; Miller, N. E.

doi:10.1016/s0140-6736(86)91222-5

Cited by 202 publications

(78 citation statements)

References 12 publications

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“…However, in some cases, there is circumstantial evidence that suggests sequencing errors. At codon 766, Law et al 8 observed CGA, whereas all other authors observed CAG; at codon 1391, Cladaras et al 9 observed TCT, whereas all others observed TTC; at codon 2298, Hardman et al 50 observed TAT, whereas all others observed ATT; at codon 2906, Law et al 8 observed TCG, whereas all others observed TGC; at codon 3264, Carlson et al 51 observed CTG, whereas all others observed CGT; at codon 3404, Law et al 8 observed CCG, whereas all others observed GCC; and at codon 3797, Cladaras et al 9 observed CGA, whereas all others observed CAG. In each of these cases, the differences involve the rearrangement of two or three nucleotides, a situation that is unlikely to have arisen by point mutation.…”

Section: Variations Among Apoproteln B-100 Sequences From Different Lmentioning

confidence: 95%

“…Some of the sequence variations have also been detected as restriction fragment polymorphisms in population studies. For example, the variation at codon 2488 gives rise to an Xba I polymorphism 50 and at codon 4154, an AAA codon to a GAA codon change results in an EcoR I site polymorphism. 51 We also note from Figure 8 that 12 of the sequence differences have been reported by more than one laboratory; two (codons 2488 and 4145) have been noted above, and the others are codons 71, 591, 2285, 3292, 3400, 3405, 3705, 3849, 3922, and 3937.…”

Section: Variations Among Apoproteln B-100 Sequences From Different Lmentioning

confidence: 99%

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Structure of apolipoprotein B-100 of human low density lipoproteins.

et al. 1989

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We have analyzed low density lipoproteins (LDL) apolipoprotein (apo) B structure by direct sequence analysis of LDL apo B-100 tryptlc peptides. Native LDL were digested with trypsin, and the products were fractionated on a Sephadex G-50 column. The partially digested apo B-100 still associated with liplds was recovered In the void volume (designated trypsln-nonreleasable, TN, peptides). The released peptides (designated trypsln-releasable, TR, peptides) in subsequent peaks were repurifled on two successive high-performance liquid chromatogaphy (HPLC) columns. The TN peak was dellpidated and redigested with trypsin, and the resulting peptides were purified on two successive HPLC columns. Using this approach, we sequenced over 88% of LDL apo B-100, extending and refining our previous study (Nature 1986;323:738-742) which covered 52% of the protein. TN peptides made up 31%, and the TR peptides, 34% of the apo B-100 sequence; 23.7% were found under both TN and TR categories. Based on its differential trypsin releasabllity, apo B-100 can be divided into five domains: 1) residues 1-1000, largely TR; 2) residues 1001-1700, alternating TR and TN; 3) residues 1701-3070, largely TN; 4) residues 3071-4100, mainly TR and mixed; and 5) residues 4101-4536, almost exclusively TN. Domain 1 contained 14 of the 25 Cys residues In apo B. Domain 4 encompassed seven N-glycosylatIon sites, and contained the putative receptor binding domains. All 19 potential N-glycosylatlon sites were directly sequenced: 16 were found to be glycosylated and three were not Three pairs of dlsurfide bridges were also mapped. Finally, a combination of cDNA sequencing, direct mRNA sequencing, and comparison of published apo B-100 sequences allowed us to Identify specific amino acid residues within apo B-100 that seem to represent bona fide allellc variations. Our study provides information on LDL apo B-100 structure that will be important to our understanding of its conformation and metabolism. (Arteriosclerosis 9:96-108, January/February 1989) L ow density lipoproteins (LDL) are the major carriers of cholesterol in plasma, and their increased concentration in circulation is correlated with the development of atherosclerosis. 12 In normal individuals, very low density lipoproteins (VLDL) are the major precursor lipoproteins of plasma LDL. LDL are removed from the circulation by both high-affinity receptor-mediated 3 and receptor-independent 4 pathways, the liver being the major organ responsible for LDL clearance. Apoprotein (apo) B-100 is the major protein constituent in LDL and is the ligand recognized by the LDL receptor.The complete sequence of apo B-100 has been recently deduced from its cDNA sequence. 5 -8 It is one of the largest monomeric proteins known, with a calculated

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Section: Variations Among Apoproteln B-100 Sequences From Different Lmentioning

confidence: 95%

Section: Variations Among Apoproteln B-100 Sequences From Different Lmentioning

confidence: 99%

Structure of apolipoprotein B-100 of human low density lipoproteins.

et al. 1989

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“…Although not associated previously with PE or CHT, an APOB polymorphism (Thr2488Thr, CϾT) was added to the list of candidate polymorphisms for both diseases. The rationale for testing this polymorphism for PE consists in its association with serum level of LDL and apolipoprotein B 41,42 and the link between preeclampsia and increased serum concentration of small dense LDL. 4 For chronic essential hypertension, the rationale was based on the fact that an association of another polymorphism of APOB with blood pressure was reported previously.…”

Section: Association Study Of Candidate Genesmentioning

confidence: 99%

Implication of an AGT Haplotype in a Multigene Association Study With Pregnancy Hypertension

et al. 2004

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Abstract-Several association studies of candidate genes for preeclampsia and essential hypertension have led to discordant results, partly because of small sample sizes. Using a large population-based sample of pregnant women, we conducted an association study of 10 polymorphisms in 9 genes and aimed (1) to validate 10 published associations with preeclampsia or essential hypertension, (2) to investigate candidate polymorphisms previously associated with preeclampsia for association with essential hypertension and similarly with polymorphisms previously associated with essential hypertension. From a prospective sample of 3391 nulliparous French Canadian pregnant women, we identified 180 cases of preeclampsia, 203 cases of essential hypertension that were matched with normotensive control subjects (nϭ310 and 357, respectively). Polymorphisms were genotyped by allele-specific PCR. Among our candidate polymorphisms, the Met allele of Thr174Met of AGT was associated with preeclampsia (Pϭ0.0033). Haplotype analysis revealed that the A-Met-Thr (G1035A-Thr174Met-Met235Thr) haplotype was associated with a 2.1-fold increased risk of preeclampsia (95% CI, 1.4 to 3.4; Pϭ0.0008). In conclusion, we observed a strong association between a specific AGT haplotype and preeclampsia in our population, without replicating previous published associations with either preeclampsia or essential hypertension. Our data support a role for AGT in genetic susceptibility to preeclampsia.

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“…The presence of thymine creates a restriction site for the XbaI enzyme characterizing the X+ allele, whereas its absence determines the X-allele. These are synonymous variations and so they do not affect the amino acid sequence of apo B (2)(3)(4). The EcoRI polymorphism of the apo B gene ap-…”

Section: Introductionmentioning

confidence: 99%

The X-X-/E+E+ genotype of the XbaI/EcoRI polymorphisms of the apolipoprotein B gene as a marker of coronary artery disease in a Brazilian sample

Scartezini

Zago

Chautard‐Freire‐Maia

et al. 2003

Braz J Med Biol Res

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Studies that consider polymorphisms within the apolipoprotein B (apo B) gene as risk factors for coronary artery disease (CAD) have reported conflicting results. The aim of the present study was to search for associations between two DNA RFLPs (XbaI and EcoRI) of the apo B gene and CAD diagnosed by angiography. In the present study we compared 116 Brazilian patients (92 men) with CAD (CAD+) to 78 control patients (26 men) without ischemia or arterial damage (CAD-). The allele frequencies at the XbaI (X) and EcoRI (E) sites did not differ between groups. The genotype distributions of CAD+ and CAD-patients were different (c 2(1) = 6.27, P = 0.012) when assigned to two classes (X-X-/E+E+ and the remaining XbaI/EcoRI genotypes). Multivariate logistic regression analysis showed that individuals with the X-X-/E+E+ genotype presented a 6.1 higher chance of developing CAD than individuals with the other XbaI/EcoRI genotypes, independently of the other risk factors considered (sex, tobacco consumption, total cholesterol, hypertension, and triglycerides). We conclude that the X-X-/E+E genotype may be in linkage disequilibrium with an unknown variation in the apo B gene or with a variation in another gene that affects the risk of CAD.

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Common Dna Polymorphism Within Coding Sequence of Apolipoprotein B Gene Associated With Altered Lipid Levels

Cited by 202 publications

References 12 publications

Structure of apolipoprotein B-100 of human low density lipoproteins.

Structure of apolipoprotein B-100 of human low density lipoproteins.

Implication of an AGT Haplotype in a Multigene Association Study With Pregnancy Hypertension

The X-X-/E+E+ genotype of the XbaI/EcoRI polymorphisms of the apolipoprotein B gene as a marker of coronary artery disease in a Brazilian sample

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