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Polymorphism of methylenetetrahydrofolate reductase gene (Mthfr) and occurrence of the hyperhomocyteinemia-related diseases

100%

Pawlak A. L., Strauss E., Pawlak A. L.

Postępy Higieny i Medycyny Doświadczalnej

2001

vol. 55

issue 2

233-256

Methylenetetrahydrofolate reductase (MTHFR), is a cytosolic enzyme, the product of which is N5-metyltetrahydrofolate, the main form of folates in tissues and the carbon donor for methylation of homocysteine to methionine. In MTHFR gene a series of the pathogenic mutations is known which lead to loss of enzymatic activity as well as the two polymorphic alleles (MTHFR 677T and 1298C) with products displaying the lowered enzyme activity resulting in hyperhomocysteinaemia. These polymorphic alleles of MTHFR represent the main genetic factor contributing to hyperhomocysteinaemia. The better known allele MTHFR 677T is found in different populations with frequency between ca. 0,1 and 0,36. In persons inheriting the variant alleles of MTHFR the increase in the level of homocysteine is noted resulting in the increased susceptibility to vascular diseases and the neural tube defects in the progeny. The procedure recommended for the prevention of effects of deficiency of MTHFR activity consists of the supplementation of the diet with 0,4 mg of folic acid daily.

Increased risk of the abdominal aortic aneurysm in carriers of the MTHFR 677T allele

63%

Strauss E., Waliszewski K., Gabriel M., Zapalski S., Pawlak A. L.

Journal of Applied Genetics

2003

vol. 44

issue 1

85-93

Abdominal aortic aneurysm (AAA) presents itself as a progressive dilation of the abdominal aorta, leading ? if untreated ? to rupture. It is a common disease of the elderly, with a complex etiology. Several genetic, biochemical and environmental factors are recognized as relevant for the pathogenesis of AAA. We determined the polymorphism of the MTHFR (methylenetetrahydrofolate reductase) gene within the fourth exon (C677T) in 63 patients with AAA and compared it to that in 75 subjects of the population sample. The frequencies of the C/C, C/T and T/T genotypes were 65%, 27%, and 8% in the population sample and 33%, 60%, and 6% in the patients. This corresponds to a 4.4-fold greater risk of AAA in subjects who have the 677C/T variant of MTHFR, as compared with those who are 677C/C (p<0.0001; 95% CI=2.11-9.34). The frequency of allele MTHFR 677T in patients (0.37) was higher than in the population sample (0.21; p < 0.007). This association between the common allele of the MTHFR gene ? MTHFR 677T ? and the development of AAA suggests that elevated homocysteine (Hcy) may disturb the function of the aortic wall. The disturbance may involve enhancement of elastin degradation, the process enhanced by mild hyperhomocysteinemia in minipigs. The magnitude of this effect, which refers to the AAA patients unselected for familial occurrence, indicates that the disturbance of aortic wall physiology caused by the presence of the MTHFR 677T allele is greater than the effect of the earlier described allele disequilibrium at the polymorphic alleles of the PAI1 (plasminogen activator inhibitor 1) gene seen only in familial cases of AAA.

Familial polyposiscoli inducing mutatios in APC gene in Poland

54%

Pawlak A. L., Plawski A., Smoczkiewicz P., Kwiatkowska J., Meissner W., Krokiewicz P., West S. P.

vol. 38

issue 1

77-85

Screening for molecular changes within the adenomatous polyposis coli (APC) gene, exons 11 14 and the 5' half of exon 15, encompassing the mutation cluster region within exon 15, was performed in 30 patients with Familial Polyposis Coli (FAP). All patients were studied by heteroduplex analysis (HA) and single strand conformation polymorphism (SSCP) and molecular changes were found in 7 cases. Protein truncation test (PTT) has been performed in 17 cases in which mutations have not been found earlier, and shortening of protein product was noted in 2 cases. In three cases common deletion of 5 bp at codon 1309 and in one 5 bp deletion at codon 1061 were found. In other cases the molecular changes were demonstrated as heteroduplexes in exon 14 (1 patient), in segments E and F (one patient each) of exon 15, and in two cases the heteroduplexes were within the overlapping sequences of segments E/F and F/G of exon 15, respectively. In families where the molecular changes were found by HA, 7 persons at high risk for FAP were found and advised to undergo regular endoscopic examinations. In three persons at risk the transfer of mutation was excluded.

Refine search results

2 Journal of Applied Genetics

1 Postępy Higieny i Medycyny Doświadczalnej

1 2003

1 2001

1 1997

3 Pawlak A. L.

2 Strauss E.

1 Gabriel M.

1 Krokiewicz P.

1 Kwiatkowska J.

1 Meissner W.

1 Plawski A.

1 Smoczkiewicz P.

1 Waliszewski K.

1 West S. P.

1 Zapalski S.

Search results

Polymorphism of methylenetetrahydrofolate reductase gene (Mthfr) and occurrence of the hyperhomocyteinemia-related diseases

Increased risk of the abdominal aortic aneurysm in carriers of the MTHFR 677T allele

Familial polyposiscoli inducing mutatios in APC gene in Poland