Insulin-like growth factor-I gene polymorphism and risk of heart failure (the Rotterdam Study).
ABSTRACT We studied 4,963 participants of the population-based Rotterdam Study and found that a genetically determined chronic exposure to low insulin-like growth factor-I (IGF-I) levels is associated with an increased risk for heart failure in elderly patients.
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ABSTRACT: Heart failure accounts for a significant portion of heart diseases. Molecular mechanisms gradually emerge that participate in pathways leading to left ventricular dysfunction in common systolic heart failure (SHF) and diastolic heart failure (DHF). A human genome-wide association study (GWAS) identified two markers for SHF and no GWAS on DHF has been documented. However, genetic analyses in rat models of SHF and DHF have begun to unravel the genetic components known as quantitative trait loci (QTLs) initiating systolic and diastolic function. A QTL for systolic function was detected and the gene responsible for it is identified to be that encoding the soluble epoxide hydrolase. Diastolic function is determined by multiple QTLs and the Ccl2/monocyte chemotactic protein gene is the strongest candidate. An amelioration on diastolic dysfunction is merely transient from changing such a single QTL accompanied by a blood pressure reduction. A long-term protection can be achieved only via combining alleles of several QTLs. Thus, distinct genes in synergy are involved in physiological mechanisms durably ameliorating or reversing diastolic dysfunction. These data lay the foundation for identifying causal genes responsible for individual diastolic function QTLs and the essential combination of them to attain a permanent protection against diastolic dysfunction, and consequently will facilitate the elucidation of pathophysiological mechanisms underlying hypertensive diastolic dysfunction. Novel pathways triggering systolic and diastolic dysfunction have emerged that will likely provide new diagnostic tools, innovative therapeutic targets and strategies in reducing, curing and even reversing SHF and DHF.Journal of Hypertension 11/2014; 33(1). DOI:10.1097/HJH.0000000000000400 · 4.22 Impact Factor
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ABSTRACT: Insulin-like growth factor-I (IGF-I) plays an important role in the growth and development of vertebrates. To study polymorphisms of IGF-I, we screened a total of 4555 bp of genomic sequences in four exons and partial introns for the discovery of single nucleotide polymorphism (SNP) in common carp (Cyprinus carpio). Three SNPs (g.3759T>G, g.7627T>A and g.7722T>C) in intron 2 and a nonsynonymous SNP (g.7892C>T) in exon 3 were identified in a pilot population including random parents and their progenies. 289 progenies were further genotyped for studying possible associations between genotypes or combined genotypes and growth traits. The results showed that the locus g.7627T>A was significantly associated with body weight and body length, and fish with genotype AA had a mean body weight 5.9% higher than those with genotype TT. No significant associations were observed between genotypes of other loci and growth traits. However, when both g.7627T>A and g.7722T>C were considered, the combined genotype TT/TT was extremely associated with the lowest values of body length and body weight and the highest K value in comparison with other diplotypes (p < 0.01). These results suggest that genotype AA at g.7627T>A and its combined genotypes with alleles from another locus have positive effects on growth traits, which would be a candidate molecular marker for further studies in marker-assisted selection in common carp.International Journal of Molecular Sciences 12/2014; 15(12):22471-22482. DOI:10.3390/ijms151222471 · 2.46 Impact Factor
Chapter: Renin-Angiotensin System[Show abstract] [Hide abstract]
ABSTRACT: Over 100 years have passed since the discovery of renin as a “pressor substance” in 1898 by Robert Tigerstedt at Karolinska Institute. The 48-page publication “Niere und Kreislauf” in Skandinävisches Archiev für Physiologie in 1898 by Tiegerstedt and Bergman detailed their meticulous approaches, even including the design of a flow meter to measure blood pressure changes and documentation of long-lasting pressor effects of renin and tachyphylaxis (1). The kidney became the target of studies again 30 some years later in independently conducted studies by Goldblatt, a pathologist who succeeded in making a dog model of renovascular hypertension by constricting the renal artery with silver clips. This work is based on Goldblatt’s repeated observations that renal arterial stenosis frequently accompanies hypertension. He also found that venous plasma of ipsilateral kidney contains a vasopressor substance (2). Study of renin-angiotensin was given a solid base when renin was found to be a peptidase that produces the pressor peptide angiotensin (a hybrid of angiotonin and hypertensin), demonstrated by Page and Braun-Menendez and their associates in the late 1930s. Angiotensin I (ANG I) was isolated by Skeggs et al., and the structure of angiotensin II (ANG II) was determined by Lentz et al. Its synthesis was reported by Bumpus’ and Schwyzer’s groups in 1950. Skeggs et al. discovered two forms of angiotensin and two steps of Ang II formation from angiotensinogen by way of ANG I. Skeggs’ group also discovered angiotensin-converting enzyme (ACE). Later, ACE was identified as kininase II by Erdös. This discovery by Erdös demonstrated an intimate relationship between angiotensin formation and bradykinin destruction (3).12/2008: pages 121-147;