Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.5.7.1 (methylenetetrahydrofolate reductase)
 2,116 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We analyzed the evolution with age of the frequencies of the I/D polymorphism of the angiotensin I-converting enzyme (ACE), a1166c of the angiotensin II AT1 receptor (AT1R), M235T of the angiotensinogen (AGT) and A225V of their methylenetetrahydrofolate reductase (MTHFR) gene in a healthy (H) population and the subsequent comparison to age- and sex-matched groups of myocardial infarction (MI) subjects. A total of 472 H subjects were divided into three groups < 30, 30-55 and > 55 years old and 277 individuals with MI into two groups 30-55 and > 55 years old. The evolution with age showed that the AGT M allele (P < 0.001) and the MTHFR V allele (P < 0.05) frequency decreased with age in H men. The comparison between healthy and MI groups showed that the MM genotype frequency increased in MI men > 55 years (OR =4.16; 95% CI; 1.72-10.1) The cc genotype showed a similar behaviour (OR = 3.96; 95% CI; 1.21-12.9). In men, all the combinations with MM genotype presented a high risk, with OR values between 1.10 and 7.22. In women, the cc genotype increased in the MI > 55 group (OR = 6.66; 95% CI; 2.02-21.9). All the combinations with the cc genotype showed OR values between 1.71 and 13.3. The MM genotype in men and cc genotype in men and women, are independent risk factors for MI. We propose that the study of the allele frequency evolution in an H population at different ages is essential to determine risk factors for MI in case-control studies, since data from isolated age-matched groups can be misinterpreted.
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PMID:The genotype interactions of methylenetetrahydrofolate reductase and renin-angiotensin system genes are associated with myocardial infarction. 1048 56

Recent developments in molecular biological techniques allowed us to examine the genetic risk factors responsible for essential hypertension. The candidate gene approach revealed that several gene polymorphisms increase the relative risk for hypertension. Most genetic studies, however, examined only young subjects but not elderly ones. To examine the importance of gene polymorphisms in elderly hypertension, we carried out a case-control study and compared the odds ratio for hypertension between young (< 60) and elderly (> or = 60) subjects. The participants of this study were recruited from the outpatients of Osaka University Medical School with informed consent. We examined the following polymorphisms as candidates: the angiotensinogen (AGT/M235T), angiotensin converting enzyme (ACE I/D), angiotensin II type 1 (AT1/A1166C) and type 2 (AT2/C3123A) receptors, alpha-adducin (adducin/Gly460Trp), methylenetetrahydrofolate reductase (MTHHR/C677T), and apolipoprotein (apoE/epsilon 4, apoE/T-491A). In young subjects, the AGT/T235 allele significantly increased the odds ratio for hypertension but not in elderly subjects. In young males, the AT2/A3123 allele was also associated with hypertension but not in females or in elderly subjects. Other associations between polymorphism and hypertension did not reach a significant level. To sum up, it was revealed that some polymorphisms increase the susceptibility for hypertension but others do not, which suggests that there is heterogeneity in the genetic involvement of polymorphism due to aging.
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PMID:[Genetic analysis of candidate gene polymorphisms in elderly hypertension]. 1055 62

It is most unlikely that there is a single 'pre-eclampsia (PE) gene'. We are probably looking for a cluster of polymorphisms which, possibly in conjunction with environmental factors, predispose to the development of the condition. Accurate phenotyping is vital for any genetic studies of PE, and since the disease is only clinically-detectable in the second half of pregnancy, is particularly difficult. It is increasingly likely that there is a fetal genetic contribution which can only be examined after birth. Candidate genes examined on the basis of displayed or hypothetical pathophysiological effects, but for which no evidence of association or linkage has been found have included HLA-DRbeta, HLA-G, and tumour necrosis factor alpha (chromosome 6), angiotensin-converting enzyme (chromosome 17) and CuZn superoxide dismutase (chromosome 21). Chromosomal exclusion mapping and a pedigree study suggest a role for genes on chromosomes 1, 3, 4, 9 or 18. Two genes concerned with clotting, those for factor 5 and methylenetetrahydrofolate reductase, lie on chromosome 1. Both have polymorphisms present in significantly higher frequency in women with PE, as well as showing functional abnormality. They probably predispose to the development of the condition, without being necessary for it. The angiotensinogen (Aogen) gene also lies on chromosome 1. The renin-angiotensin system may be activated during the early stages of PE and subsequently suppressed. In some populations, a relatively common polymorphism is present in raised frequency in women with PE, but it is also raised in non-pregnant hypertensive subjects. However, it is in partial linkage disequilibrium with another polymorphism which shows significantly distorted transmission from mother to fetus in PE pregnancies. Furthermore, its expression is significantly raised in the decidual spiral arteries; abnormal placentation is a feature of PE. We have also shown that a relatively common polymorphism in the angiotensin AT1 receptor gene (chromosome 3) is associated with raised density of the receptor. Thus far, studies of candidate genes have been on a small scale and have very much reflected the pathophysiological research interests of the investigators. The multifaceted nature of PE and the difficulties of accurate phenotyping require the accumulation of a large, very carefully phenotyped, database. It is hoped that funding will become available this year in the UK to allow the collection of such a database. The introduction of chip technology should allow genome scanning of the resource.
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PMID:What is the place of genetics in the pathogenesis of pre-eclampsia? 1056 60