The c.419-420insA in the MTP gene is associated with abetalipoproteinemia among French-Canadians

Berthier, Marie-Thérèse; Couture, Patrick; Houde, Alain; Paradis, Ann-Marie; Sammak, Alya’a; Verner, Andrei; Depres, Jean-Pierre; Gagné, Claude; Gaudet, Daniel; Vohl, Marie‐Claude

doi:10.1016/j.ymgme.2003.11.001

Cited by 22 publications

(11 citation statements)

References 19 publications

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“…Eleven polymorphisms were identified, and three of them, c.933C>A, c.969 T>C, and c.2884G>C, were newly discovered (Berthier et al 2004) (Fig. 1).…”

Section: Resultsmentioning

confidence: 99%

“…To do so, we compared mRNA sequences of each exons of MTP found in the nucleotides site (http://www.ncbi.nlm.nih.-gov/entrez/query.fcgi/nucleotide) with a genomic DNA sequence (accession number: gi:18098543). Intronic primers were designed using the Primer 3.0 software (http://wwwgenome.wi.mit.edu/cgibin/primer/primer3.cgi), as previously described (Berthier et al 2004).…”

Section: Lipoprotein and Lipid Measurementsmentioning

confidence: 99%

“…The promoter region and the 18 exons were amplified from genomic DNA by the use of specific primers, with the adequate annealing temperature (Berthier et al, 2004). PCR reaction volume was 50 ll, and conditions were as follows: 1.25 U AmpliTaqDNA polymerase (Perkin-Elmer Cetus) in the buffer recommended by the manufacturer, 1.5 mM of MgCl 2 , 0.2 mM dNTPs, primers at final concentration of 0.8 lM, and 100 ng of genomic DNA.…”

Section: Lipoprotein and Lipid Measurementsmentioning

confidence: 99%

“…The corresponding restriction enzyme was chosen, as previously described (Berthier et al 2004). Digestion products were size-separated on 8% polyacrylamide gel (for c.383 T>C, c.891C>G, c.2884G>C, c.À400A>T, c.À164 T>C polymorphisms), 20% polyacrylamide electrophoresis gel (c.À493G>T polymorphism), or 4% agarose gel (c.282G>C, c.453 T>C, c.933C>A, c.969 T>C, c.1151A>C polymorphisms) according to differences in fragment sizes, subsequently stained with ethidium bromide, and pictured on a UV light box.…”

Section: Detection Of Sequence Variationsmentioning

confidence: 99%

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Molecular screening of the microsomal triglyceride transfer protein: association between polymorphisms and both abdominal obesity and plasma apolipoprotein B concentration

et al. 2004

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Microsomal triglyceride transfer protein (MTP) plays a critical role in the assembly of lipoproteins. The aim of this study was first to seek new MTP gene variants and then to verify whether MTP gene polymorphisms were associated with plasma lipoprotein/lipid levels in men with visceral obesity. Molecular screening of the MTP gene revealed 11 polymorphisms. The carriers of the c.933A allele and c.1151C allele or À400A/A homozygotes were characterized by increased levels of abdominal visceral adipose tissue (AT) measured by computed tomography (P=0.02, P=0.04, P=0.03, respectively). After dividing each genotype group into subgroups using 130 cm 2 as a cutoff point for visceral AT, significantly higher low-density lipoprotein (LDL)-apolipoprotein B (apoB) concentrations were found in obese men bearing the c.891G allele, the À400 T allele, as well as for 282G/G homozygotes, 933C/C homozygotes, and 1151A/A homozygotes when compared to their lean counterparts. Haplotypes were not associated with phenotypes under study. In conclusion, some MTP gene polymorphisms in the French Canadian population are associated with the amount of abdominal visceral AT and plasma LDL-apoB concentrations.

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“…Eleven polymorphisms were identified, and three of them, c.933C>A, c.969 T>C, and c.2884G>C, were newly discovered (Berthier et al 2004) (Fig. 1).…”

Section: Resultsmentioning

confidence: 99%

Section: Lipoprotein and Lipid Measurementsmentioning

confidence: 99%

Section: Lipoprotein and Lipid Measurementsmentioning

confidence: 99%

Section: Detection Of Sequence Variationsmentioning

confidence: 99%

See 2 more Smart Citations

Molecular screening of the microsomal triglyceride transfer protein: association between polymorphisms and both abdominal obesity and plasma apolipoprotein B concentration

et al. 2004

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“…The majority of the mutations reported following sequence analysis of the MTP gene or cDNA in ABL subjects are frameshift, nonsense, and splice site mutations that are predicted to encode truncated forms of MTP completely devoid of function (20)(21)(22)(23)(24)(25)(26)(27)(28). However, a few missense mutations, R540H ( 23,25 ), S590I ( 25,29 ), N780Y ( 7,26 ), D384A ( 23,30 ), and G746E ( 25 ) have been described.…”

Section: Immunofl Uoroscencementioning

confidence: 99%

Loss of both phospholipid and triglyceride transfer activities of microsomal triglyceride transfer protein in abetalipoproteinemia

Khatun

Walsh

Hussain

2013

Journal of Lipid Research

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A severe form of abetalipoproteinemia caused by new splicing mutations of microsomal triglyceride transfer protein (MTTP)

et al. 2011

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Abetalipoproteinemia is a rare autosomal recessive disease characterized by low lipid levels and by the absence of apoB-containing lipoproteins. It is the consequence of microsomal triglyceride transfer protein (MTTP) deficiency. We report two patients with new MTTP mutations. We studied their functional consequences on the triglyceride transfer function using duodenal biopsies. We transfected MTTP mutants in HepG2 and HeLa cells to investigate their association with protein disulfide isomerase (PDI) and their localization at the endoplasmic reticulum. These children have a severe abetalipoproteinemia. Both of them had also a mild hypogammaglobulinemia. They are compound heterozygotes with c.619G4T and c.1237À28A4G mutations within the MTTP gene. mRNA analysis revealed abnormal splicing with deletion of exon 6 and 10, respectively. Deletion of exon 6 (D6-MTTP) introduced a frame shift in the reading frame and a premature stop codon at position 234. Despite the fact that D6-MTTP and D10-MTTP mutants were not capable of binding PDI, both MTTP mutant proteins normally localize at the endoplasmic reticulum. However, these two mutations induce a loss of MTTP triglyceride transfer activity. These two mutations lead to abnormal truncated MTTP proteins, incapable of binding PDI and responsible for the loss of function of MTTP, thereby explaining the severe abetalipoproteinemia phenotype of these children.

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The c.419-420insA in the MTP gene is associated with abetalipoproteinemia among French-Canadians

Cited by 22 publications

References 19 publications

Molecular screening of the microsomal triglyceride transfer protein: association between polymorphisms and both abdominal obesity and plasma apolipoprotein B concentration

Molecular screening of the microsomal triglyceride transfer protein: association between polymorphisms and both abdominal obesity and plasma apolipoprotein B concentration

Loss of both phospholipid and triglyceride transfer activities of microsomal triglyceride transfer protein in abetalipoproteinemia

A severe form of abetalipoproteinemia caused by new splicing mutations of microsomal triglyceride transfer protein (MTTP)

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