Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0012872 (DNA marker)
 929 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Twelve unrelated subjects with heterozygous familial defective apolipoprotein B-100 were identified in a group of 252 patients with type IIa hypercholesterolaemia. Approximately 5% of hypercholesterolaemia can be explained by this mutation in the collective studied. Familial defective apolipoprotein B-100 is therefore the most common known mutation causing primary hypercholesterolaemia. Family studies revealed an additional 14 affected subjects. All family members with the mutation had elevated cholesterol concentrations. In a normolipidaemic control group of 146 subjects the mutation was not present. In the affected individuals a variable expression of total cholesterol concentrations and atherosclerosis was observed. Plasma cholesterol ranged from 6.60 to 14.89 mmol/l with a mean of 9.43 mmol/l. Premature atherosclerosis was present in 4 patients, while one affected woman is now 92 years old and has no symptoms of coronary heart disease or peripheral atherosclerosis. Analysis of the haplotypes and genotypes by 3 biallelic and 1 multi-allelic DNA marker suggests that the disorder is caused in all affected patients by the same rare allele. The fact that the same mutant allele was also identified in other European populations and in a North American population of Caucasian origin argues for a common European origin of this mutation.
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PMID:Familial defective apolipoprotein B-100 in 12 subjects and their kindred. 148 44

Nitric oxide (NO) synthesized by the vascular endothelium regulates mammalian blood vessels and other systems in humans. Recently, an endothelial nitric oxide synthase (ecNOS) gene polymorphism, the 27-bp repeat in intron 4 (ecNOS4), was reported to be related to the pathogenesis of coronary heart disease and terminal renal failure. We analyzed this polymorphism in a group of 413 healthy subjects, and measured their plasma nitrite and nitrate (NOx) levels. The frequency of the b allele was 89.8% , and the frequency of the a allele was 10.2%. The frequency of ecNOS4 b/b, ecNOS4 b/a, and ecNOS4 a/a in the healthy subjects in this study was 0.814 (n=336), 0.169 (n=70) and 0.017 (n=7), respectively. Using this polymorphism as a DNA marker, we found a strong association between the alleles of the ecNOS gene polymorphism and the plasma NOx levels. The basal NO metabolite levels were 28.8 micromol/L in subjects with ecNOS4 a/a, 31.4 micromol/L in those with ecNOS4 b/a, and 35.5 micromol/L in those with ecNOS4 b/b. The mean plasma NOx level of the subjects who were homozygous for the a allele was nearly 20% lower than in the subjects with the b allele. The plasma NOx level of the subjects with the a allele was 31.2+/-2.00 micromol/L, and significantly lower than the 35.5+/-0.93 micromol/L in those without the a allele (P <0.05). The results of this study indicate that the ecNOS4 gene locus may be responsible for variations in the genetic control of plasma NOx and that analysis of ecNOS4 gene polymorphism may be a useful tool for studying the relation between NO and diseases.
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PMID:Evidence of association of the ecNOS gene polymorphism with plasma NO metabolite levels in humans. 953 6

Adducin is a heterodymeric cytoskeleton protein, the 3 subunits of which are encoded by genes (ADD1, ADD2, ADD3) mapping to 3 different chromosomes. A long series of parallel studies in the Milan hypertensive rat strain model of hypertension and humans indicated that an altered adducin function may cause hypertension through an enhanced constitutive tubular sodium reabsorption. Six human linkage studies showed positive results when a DNA marker mapping to 30 kb from the ADD1 locus or single-nucleotide polymorphisms (SNPs) of 1 of the 3 adducin genes were considered either alone or in combination with each other or angiotensin-converting enzyme (ACE) D allele or salt intake. When DNA markers mapping at much larger distance from the ADD1 locus were used, negative results were found by 4 studies. Positive results were also obtained in 18 of 20 association studies that, in addition to blood pressure, investigated variables reflecting body sodium or the renin-angiotensin system. Mixed results regarded case-control studies or studies in predominantly normotensive populations that did not consider the above-mentioned variables. Four of 5 studies showed a selective beneficial effect of diuretics in carriers of the mutated ADD1. Twelve of 16 studies found that ADD1 polymorphism alone or in combination with that of ACE positively associates with stroke or coronary heart disease or renal or vascular dysfunctions. In conclusion, when context is taken into account, the impact of adducin in hypertension and its related disorders is clear.
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PMID:Adducin polymorphism: detection and impact on hypertension and related disorders. 1569 49