Genomics in the Scientific Literature [14] Cardiovascular Disease

Genomics in the Scientific Literature
Topics in the Scientific Literature

Cardiovascular Disease

1. Genetics and cardiac channelopathies
Campuzano O, et al.
Genet Med 2010 Apr

Genet Med. 2010 Apr 8. [Epub ahead of print]

Genetics and cardiac channelopathies.
Campuzano O, Beltrán-Álvarez P, Iglesias A, Scornik F, Pérez G, Brugada R.

From the Cardiovascular Genetics Center, UdG-IdIBGi, University of Girona, Girona, Spain.

Abstract
Sudden cardiac death is a major contributor to mortality in industrialized nations; in fact, it is the cause of more deaths than acquired immune deficiency syndrome, lung and breast cancer, and stroke together. Frequently, the autopsy becomes the principal diagnostic tool because macroscopic and microscopic analyses reveal the underlying cause of death. However, a significant number of sudden cardiac deaths remain unexplained. These cases are referred to as "natural" or arrhythmogenic. In the young, in up to 50% of sudden cardiac death cases, sudden death is the first and only clinical manifestation of an inherited cardiac disease that had remained undetected by conventional clinical investigations. To improve diagnosis, genetic testing has recently been added to these clinical tools. During the last two decades, there has been considerable progress in the understanding about genetics of sudden cardiac death. With that new information, the probands and their family members can make an informed decision regarding their care and know whether and to what extent they are at risk of suffering from the disease. Thus, genetic technology and expertise have become essential for the diagnosis of some forms of inherited cardiac diseases and to provide a basis for subsequent prevention strategies. This review focuses on recent advances in the understanding of cardiopathies owing to genetic investigations.

PMID: 20386317 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/20386317?dopt=Abstract



2. Genetics of primary hypertension: The clinical impact of Adducin Polymorphisms
Citterio L, et al.
Biochim Biophys Acta 2010 Apr

Biochim Biophys Acta. 2010 Apr 8. [Epub ahead of print]

Genetics of primary hypertension: The clinical impact of Adducin Polymorphisms.
Citterio L, Lanzani C, Manunta P, Bianchi G.

Nephrology, Dialysis and Hypertension, San Raffaele Scientific Institute, and Chair of Nephrology, Università "Vita-Salute" San Raffaele, Milan, Italy.

Abstract
The usefulness of the results so far published on genetics of primary hypertension for establishing the clinical impact of candidate gene polymorphisms is weakened by the scanty information regarding: Of course, not all these informations are available for adducin polymorphisms. In this review, being aware of their importance, the evaluation of the clinical impact of adducin has been focused on data obtained together with the interacting genetic-environmental or biological factors. Adducin polymorphisms and Endogenous Ouabain (EO) were detected by a top-down approach in rodents after having demonstrated, at cellular and kidney level, that an increase in tubular Na reabsorption could underlies the transition from normotension to hypertension both in rodents and humans. Therefore, we hypothesized that adducin polymorphisms and EO may operate within the triggering RGN that initiates the increase in blood pressure in both species. The distinction between triggering RGN and the secondary RGN is important both to limit the level of genetic complexity arising from secondary changes, and to detect the molecular target to develop tailored therapeutic approach. The pharmacogenomic approach, both in rodents or humans, with newly discovered and never treated hypertension, may be useful to strengthen the "causation" of genetic mechanism. Mutant adducin increases tubular reabsorption: diuretics, because of their effect on overall tubular reabsorption, or rostafuroxin, because of its selective inhibition of the adducin and ouabain effects, may be used for this purpose. Indeed the pharmacogenomic approach with both drugs have provided data consistent with the role of adducin and EO. Taken together, all these findings indicate a clear impact of adducin polymorphism and EO in a subset of patients when the appropriate environmental, biological or genetic context is taken into account. The size of this impact is variable and affected by the context. Copyright © 2010. Published by Elsevier B.V.

PMID: 20382219 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/20382219?dopt=Abstract


3. Genome-wide association analysis of total cholesterol and high-density lipoprotein cholesterol levels using the Framingham Heart Study data
Ma L, et al.
BMC Med Genet 2010 Apr;11(1):55
BMC Med Genet. 2010 Apr 6;11(1):55. [Epub ahead of print]

Genome-wide association analysis of total cholesterol and high-density lipoprotein cholesterol levels using the Framingham Heart Study data.
Ma L, Yang J, Runesha HB, Tanaka T, Ferrucci L, Bandinelli S, Da Y.

Abstract
ABSTRACT: BACKGROUND: Cholesterol concentrations in blood are related to cardiovascular diseases. Recent genome-wide association studies (GWAS) of cholesterol levels identified a number of single-locus effects on total cholesterol (TC) and high-density lipoprotein cholesterol (HDL) levels. Here, we report single-locus and epistasis SNP effects on TC and HDL using the Framingham Heart Study (FHS) data. RESULTS: Single-locus effects and pairwise epistasis effects of 432,096 SNP markers were tested for their significance on log-transformed TC and HDL levels. Thirty three additive SNP effects reached single-locus genome-wide significance (p < 7.2E-8) and no dominance effect reached genome-wide significance. Two new gene regions were detected, the RAB3GAP1-R3HDM1-LCT-MCM6 region of chr02 for TC identified by eight new SNPs, and the RPL21P98 (RNA gene, chr12) region for HDL identified by one new SNP. Also for TC, three SNPs identified three gene regions that were tightly linked with previously reported genes associated with TC, including rs599839 that was 10 bases upstream PSRC1 and 3.498kb downstream CELSR2, rs4245791 in ABCG8 that slightly overlapped with ABCG5, and rs632632 that was 4.5kb downstream BCAM and 65.28kb upstream TOMM40. Five reported gene regions were confirmed by this study, including CELSR2 for TC confirmed by a new SNP in CELSR2, APOB for TC by a previously reported SNP in APOB, LPL for HDL by 13 new SNPs 8-45kb downstream, CETP for HDL by two new SNPs 0.5~11kb upstream, and the LIPG-ACAA2 region for HDL by five new SNPs inside this region. Six epistasis effects of TC and twenty one epistasis effects of HDL in eight gene-region pairs had p-values < E-11. Two dominance x dominance effects of HDL between LMBRD1 (chr05) and LRIG3 region (chr12) reached the significance of genome-wide 5% type-I error with the Bonferroni correction (p < 3.266E-13). CONCLUSIONS: Genome-wide association analysis of the FHS data detected new single-locus and epistasis SNP effects on TC and HDL and confirmed some previously reported gene regions associated with TC and HDL.

PMID: 20370913 [PubMed - as supplied by publisher]Free Article
http://www.ncbi.nlm.nih.gov/pubmed/20370913?dopt=Abstract