Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Apoproteins (also known as apolipoproteins) have been studied extensively because of their role in lipid transport, association between specific genotypes and elevated serum lipid levels, and increased risk of heart disease. There is considerable genetic variation in the geographic distributions of these markers, with a north-south cline of the APOE*4 allele observed in Europe by Lucotte et al. ([1997] Hum Biol 69:253-262). This study compares the frequencies of seven APO (APOA1 -75 bp, APOA1 +83 bp, APOB Ins/Del, APOB XbaI, APOC3 SstI, and APOE) and LPL loci in Mennonite populations from Kansas and Nebraska. In total, 277 individuals were sampled from Goessel, Meridian, Garden View, and Lone Tree in 2002-2004. In addition, DNA samples that were collected in 1981 from Henderson, Nebraska, were genotyped for the seven APO and LPL loci. Of the seven APO and LPL loci tested, only one locus, APOB XbaI, departed significantly from Hardy-Weinberg equilibrium, with an unexpected excess of observed heterozygotes. The frequencies of the several APO loci are unique among the Mennonites, separating them from other European populations. A bidimensional scaling representation of Reynold's co-ancestry distances based on allelic frequencies of the seven APO and LPL markers in five Mennonite congregations fails to represent schematically the known patterns of fission. It is unclear whether the observed patterns are due to selection operating on these loci or whether genetic drift, small populations sizes, or a lack of statistical power of these biallelic loci distort the observed genetic relationship among congregations.
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PMID:Apolipoproteins (apoproteins) and LPL variation in Mennonite populations of Kansas and Nebraska. 1613 40

Although the risk for coronary heart disease (CHD) associated with single SNPs is modest it has been suggested that, in combination, several common risk-associated alleles could lead to a substantially better heart disease risk prediction. We have modelled this using 10 SNPs in ten candidate genes (APOB, NOS3, APOE, ACE, SERPINE1, MTHFR, ITGA2B, PON 1, LPL, and CETP) and their predicted summary risk estimates from meta-analysis. Based on published allele frequencies, approximately 29% of the general population would be expected to carry less than three risk alleles, approximately 55% would carry 3 or 4 risk alleles, 4% would have 6 and 1% 7 or more risk alleles. Compared to the mean of those with 3 or 4 risk associated genotypes, those with 6 and 7-or-more alleles have a significantly higher risk odds ratio (OR) of CHD (mean OR (95% Confidence Intervals), 1.70 (1.14 to 2.55); and 4.51 (2.89 to 7.04) respectively), while compared to those in the lowest decile of risk, those in the highest decile have a CHD odds ratio in the range of 3.05 (2.24 to 4.14). Taking into account age and the risk alleles carried, the mean 10 year probability for developing CHD for a 55 year old man was calculated to be 15% (8.6% to 24.8%), with nearly 1 in 5 having more than 20% risk. Whether this particular group of 10 SNPs will improve the accuracy of CHD predictions over the combination of classical risk factors in clinical use requires further experimental evidence.
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PMID:The use of meta-analysis risk estimates for candidate genes in combination to predict coronary heart disease risk. 1740 27

Familial hypercholesterolemia (FH) is caused by mutations in the genes for LDLR, APOB or PCSK9, and identification of the causative mutation provides definitive diagnosis so that the patient can be treated, their relatives tested and, therefore, premature heart disease prevented. DNA of eight unrelated individuals with clinically diagnosed FH were analyzed using a High-Resolution Melting method (HRM) for the LDLR gene (coding region, promoter and intron/exon boundaries), the APOB gene (part exon 26) and the PCSK9 gene (exon7). Variations found were sequenced and the effect on function of confirmed variants examined using predictive algorithms. Gross deletions and insertions were analysed using MLPA. Three novel LDLR variants were found, p.(S470C), p.(C698R) and c.2312-2A>C. All were predicted to be pathogenic using predictive algorithms. Three previously reported disease-causing mutations were identified (p.(G20R), p.(N272T) and p.(S286R); the latter was also carried by a hypercholesterolaemic relative. One patient carried the pathogenic APOB variant p.(R3527Q). No large LDLR deletions nor insertions were found, neither were any PCSK9 variants identified. HRM is a sensitive method for screening for mutations. While the causative mutation has been identified in 88% of these clinically defined FH patients, there appears to be a high degree of allelic heterogeneity in Croatian patients.
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PMID:Mutation detection in Croatian patients with familial hypercholesterolemia. 2313 Aug 80

Polar bears are uniquely adapted to life in the High Arctic and have undergone drastic physiological changes in response to Arctic climates and a hyper-lipid diet of primarily marine mammal prey. We analyzed 89 complete genomes of polar bear and brown bear using population genomic modeling and show that the species diverged only 479-343 thousand years BP. We find that genes on the polar bear lineage have been under stronger positive selection than in brown bears; nine of the top 16 genes under strong positive selection are associated with cardiomyopathy and vascular disease, implying important reorganization of the cardiovascular system. One of the genes showing the strongest evidence of selection, APOB, encodes the primary lipoprotein component of low-density lipoprotein (LDL); functional mutations in APOB may explain how polar bears are able to cope with life-long elevated LDL levels that are associated with high risk of heart disease in humans.
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PMID:Population genomics reveal recent speciation and rapid evolutionary adaptation in polar bears. 2484 May 50