Analysis of the Connection C677T Polymorphism Metilentetrahidrofolatreductase Gene (MTHFR) with Atherothrombotic Ischemic Stroke in Individuals of Both Sexes
About the author:
Matlay O. I.
Heading:
CLINICAL AND EXPERIMENTAL MEDICINE
Type of article:
Scentific article
Annotation:
Every year statistics notes the increasing morbidity and mortality as the result of cardiovascular disease such as stroke and myocardial infarction in the first place. Stroke depends on age, sex, region of residence, and varies from 150 – 200 cases per 100 000 of population. The most common cause of vascular brain tromboinclusive lesions is Atherothrombosis – generalized and progressing process that depends on the evolution of atherosclerotic changes in vessels. Principally the important role in the pathogenesis of atherosclerosis and its complications is endothelial dysfunction. One of the causes of chronic endothelial damage may be negative effects of excess homocysteine. The key enzymes that affect the homocysteine level is N5,N10- metilentetrahidrofolatreductase (MTHFR), that encodes a gene MTHFR. One of clinically relevant polymorphisms MTHFR gene is an option in which the amino acid residue substitution of alanine for valine residue in folate binding site (polymorphism C677T (Ala222Val) gene MTHFR, rs1801133). As the result of mutations a variant of the enzyme with a termolability threshold 55 ° C is produced, which has twice reduced activity. The aim of our study was to analyse communication polymorphism C677T MTHFR gene with atherothrombotic ischemic stroke in two sexes of Ukrainian population. For analysis venous blood of 170 patients with atherothrombotic ischemic stroke (42,4 % women and 57,6 % men) aged 40 to 85 years (mean age – 64,7 ± 0,73 years) who were on the records in the outpatient department Sumy clinical Hospital № 5 was used. The control group consisted of 124 patients (36,3 % women and 63,7 % men), average age was 76,7 ± 0,93 years. The groups did not differ in the ratio of two sexes (P = 0,294 for the І-test), but the average age of the first group (76,7 ± 0,93 years) was significantly higher than of the second one (P < 0,001). C677T polymorphism was determined by polymerase chain reaction, followed by restriction fragment length analysis. The results have been statistically worked on by using the new Excel 2000. Statistical significance of differences was determined by І and t-test. Pathogenetic variant of stroke was determined according to the criteria TOAST, based on the anamnestic data and clinical features of the disease, ultrasound Doppler data of major arteries of the head, ECG. Ischemic stroke character was determined with the help of history and clinical information of the disease given by CT brain study. Genotyping of patients with atherothrombotic ischemic stroke and the comparison of the data with the results of restriction analysis in the control group made it possible to reveal that patients with atherothrombotic ischemic stroke ratio of homozygotes for the major allele (C/C), heterozygotes (C/T) and homozygotes for the minor allele (T/T) is 52,4 %, 35,9 % and 11,8 %, while in the control group – respectively 46,0 %, 48,4 %, 5,6 %. The differences in the distribution of the frequency of these genotypes between the group of patients with atherothrombotic ischemic stroke and control groups were statistically true (P = 0,044). The Ratio of options of the same polymorphism in women and men with atherothrombotic ischemic stroke and without this disease showed the following – Women had the distribution-C / C – 51,4 %, C / T – 38,9 %, T / T – 9 7 % (in the control group, respectively 60,0 %, 35,6 %, 4,4 %), P = 0,028, respectively among men – 53,0 %, 33,7 %, 13,3 % (38,0 %, 55,7 %, 6,3 %), P = 0,011. So, in Ukrain, namely in the Sumy region, the male population who hold T/T- variant of this gene and female heterozygous (C/T) have a higher risk of atherothrombotic ischemic stroke.
Tags:
metilentetrahidrofolatreductase (MTHFR), allelic polymorphism, ischemic stroke.
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Publication of the article:
«Bulletin of problems biology and medicine» Issue 1 (106), 2014 year, 143-147 pages, index UDK 616. 831-005. 1/. 6:548. 33