Polymorphism of human transcobalamin II: Substitution of proline and/or glutamine residues by arginine

Li, Ning; Sood, Gagan; Seetharam, Shakuntla; Seetharam, Bellur

doi:10.1016/0167-4781(94)90079-5

Cited by 32 publications

(29 citation statements)

References 20 publications

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“…The Gln234Arg variant 19 was not detected in our study groups. Table 3 summarises the genotype distributions in mothers of NTD children and in controls.…”

Section: Resultsmentioning

confidence: 60%

“…19 According to ChouFasman secondary structure predictions, a tendency to form helix structures was predicted as previously described by Li et al 19 Although the helix structure was not confirmed using the GOR II algorithm, 19 we found that the latter method predicted a tendency to form turn structures. Both predictions point towards a change in secondary structure.…”

Section: Discussionmentioning

confidence: 83%

“…The previously published P259R variant 11,19 was associated with a distinct reduction in total-TC protein and apo-TC. Moreover, it was also associated with a pronounced decreased holo-TC concentration and holo-TC/total-TC ratio.…”

Section: Discussionmentioning

confidence: 99%

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Single nucleotide polymorphisms in the transcobalamin gene: relationship with transcobalamin concentrations and risk for neural tube defects

Afman¹,

Lievers²,

Put

et al. 2002

Eur J Hum Genet

102

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Homocysteine levels are elevated in mothers of neural tube defect (NTD) children, which may be due to a disturbed folate or vitamin B12 metabolism. Vitamin B12 is transported to the tissues by transcobalamin (TC). We previously showed that a low holo-TC/total-TC ratio is a risk factor for NTD, possibly due to an impaired binding of vitamin B12 to TC. The coding region of the TC gene of 12 individuals was analysed for genetic variations responsible for a disturbed vitamin B12 binding. The influence of the genetic variations observed on total-TC, holo-TC, holo-TC/total-TC, erythrocyte vitamin B12, plasma homocysteine concentrations and risk for NTD was explored in 42 mothers of a child with NTD and in 73 female controls. Direct sequencing analyses revealed five single nucleotide polymorphisms (SNPs). Three SNPs affected total-TC concentrations, whereas two SNPs seem to affect the binding of vitamin B12. None of the genotypes defined by the SNPs had a significant effect on homocysteine levels, or was associated with an increased NTD risk. Among the five SNPs observed only P259R could partly explain the reduced proportion of vitamin B12 bound to TC, which has been associated with an increased risk for having a child with NTD. Some of the variants studied affected total-TC and holo-TC/total-TC ratio but a larger study population is required to elucidate whether these SNPs influence delivery of vitamin B12 to the tissue, influence homocysteine levels and whether they are associated with an increased NTD risk.

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“…The Gln234Arg variant 19 was not detected in our study groups. Table 3 summarises the genotype distributions in mothers of NTD children and in controls.…”

Section: Resultsmentioning

confidence: 60%

Section: Discussionmentioning

confidence: 83%

See 1 more Smart Citation

Single nucleotide polymorphisms in the transcobalamin gene: relationship with transcobalamin concentrations and risk for neural tube defects

Afman¹,

Lievers²,

Put

et al. 2002

Eur J Hum Genet

102

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“…Possibly, the 259P allele a¡ects TC transcription or binding and transport of vitamin B 12 by TC with positive repercussions on intracellular availability of vitamin B 12 . 128 Other variants in the TC gene are the M198T, I219L, S376L, 113 the Q234R, 114 the I23V 115 and the G94S, S348F and R399Q. 120 The latter four were also examined by us for their possible role in homocysteine metabolism, 121 but only the I23V polymorphism seemed to have an association with homocysteine concentrations, although this was only observed in the three homozygous 23VV individuals.…”

Section: Transcobalaminmentioning

confidence: 99%

Genetics of hyperhomocysteinaemia in cardiovascular disease

2003

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Homocysteine, a sulphur amino acid, is a branch-point intermediate of methionine metabolism. It can be degraded in the transsulphuration pathway to cystathionine, or remethylated to methionine via the remethylation pathway. In both pathways, major genetic defects that cause enzyme de ciencies are associated with very high plasma homocysteine concentrations and excretion of homocystine into the urine. Mildly elevated plasma homocysteine concentrations are thought to be an independent and graded risk factor for both arterial occlusive disease and venous thrombosis. Genetic defects in genes encoding enzymes involved in homocysteine metabolism, or depletion of important cofactors or (co)substrates for those enzymes, including folate, vitamin B 12 and vitamin B 6 , may result in elevated plasma homocysteine concentrations. Plasma homocysteine concentrations are also in uenced by dietary and lifestyle factors. In the last decade, several studies have been conducted to elucidate the genetic determinants of hyperhomocysteinaemia in patients with cardiovascular disease. We report on both environmental and genetic determinants of hyperhomocysteinaemia and give a detailed overview of all the genetic determinants that have been reported to date.

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“…Elements-To identify regions that are important for the promoter activity, a series of promoter segments were cloned into a promoterless CAT reporter vector, pCAT-B, and the fusion promoter-CAT constructs were transiently transfected into human intestinal epithelial Caco-2 cells known to express endogenous TC II (20,21).…”

Section: Human Tc II Promoter Activity Is Regulated By Both Positive mentioning

confidence: 99%

Characterization of the Human Transcobalamin II Promoter

Li¹,

Seetharam²,

Seetharam³

1998

Journal of Biological Chemistry

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Polymorphism of human transcobalamin II: Substitution of proline and/or glutamine residues by arginine

Cited by 32 publications

References 20 publications

Single nucleotide polymorphisms in the transcobalamin gene: relationship with transcobalamin concentrations and risk for neural tube defects

Single nucleotide polymorphisms in the transcobalamin gene: relationship with transcobalamin concentrations and risk for neural tube defects

Genetics of hyperhomocysteinaemia in cardiovascular disease

Characterization of the Human Transcobalamin II Promoter

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