|
Group Kontula
| RESEARCH GROUP |
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Kontula Kimmo, MD, Professor |
| POST-DOCTORAL SCIENTISTS: |
| Donner Kati |
| Hiltunen Timo |
| Lehtonen Jukka |
| Miettinen Helena |
| Paavola-Sakki Paulina |
| Paukku Kirsi |
| Schalin-Jäntti Camilla |
| PhD STUDENTS: |
| Hannila-Handelberg Tuula |
| Lahtinen Annukka |
| Lappalainen Maarit |
| Lehtonen Annukka |
| Paavonen Kristian |
| Suonsyrjä Timo |
| Valli-Jaakola Kaisa |
| TECHNICIANS: |
|
Nyqvist Saara |
|
Tverin Susanna |
This group has focused on molecular genetic studies of human hypertensive and arrhythmic diseases for more than 10 years. Our previous studies have included a systematic genome-wide screen for loci linked to essential hypertension in affected non-identical twins, with subsequent identification of four chromosomal loci showing significant linkage. In addition, we showed that common variants of the epithelial sodium channel (ENaC) account for up to 9% of treatment-resistant hypertension among Finns. In future, even more attention should be paid on better phenotyping of patients, and novel intermediate phenotypes characteristic of certain subtypes of hypertension should be used to facilitate the search for the underlying genes. The GENRES Study is a pharmacogenomic study in which systematic genotype-drug response correlations will provide new information on the molecular pathogenesis of hypertension and a novel possibility to classify patients into therapeutic subclasses.
In arrhythmia research, Finnish founder gene mutations causing life-threatening disorders including long QT syndrome (LQTS) have been identified and provided data on genotype-phenotype relationships. In addition, the group recently described the clinical characteristics of an inherited cardiac disorder causing catecholamine-induced polymorphic ventricular tachycardia (CPVT) and syncope in the absence of any structural myocardial changes. We demonstrated that CPVT is caused by mutations of the cardiac calcium-release channel or ryanodine receptor type 2 (RYR2), thus delineating a new pathogenetic concept in human cardiology. In future studies, family and population-based studies will be conducted to detect modifier genes that influence phenotypic characteristics in LQTS and CPVT. Identification of the exact molecular mechanisms underlying human life-threatening ventricular arrhythmias may provide essential information, not only to pathogenesis of rare inherited arrhythmic syndromes, but also toward better understanding and novel drug treatment of ventricular tachycardias associated with more common “acquired” conditions, such as ischemia and heart failure.
REPRESENTATIVE PUBLICATIONS:
Kainulainen K, Perola M, Kaprio J, Koskenvuo K, Terwilliger J, Syvänen A-C, Vartiainen E, Peltonen L, Kontula K: Evidence for involvement of the angiotensin receptor type 1 gene locus in essential hypertension. Hypertension 33: 844-849, 1999.
Perola M, Kainulainen K, Pajukanta P, Terwilliger JD, Hiekkalinna T, Ellonen P, Kaprio J, Koskenvuo M, Kontula K, Peltonen L: Genome-wide scan of predisposing loci for elevated diastolic blood pressure in Finnish siblings. Journal of Hypertension 18: 1579-1585, 2000.
Laitinen PJ, Brown KM, Piippo K, Swan H, Devaney JM, Brahmbatt B, Donarum EA, Marino M, Tiso N, Viitasalo M, Toivonen L, Stephan DA, Kontula K: Mutations of the cardiac ryanodine receptor (RyR2) gene in familial polymorphic ventricular tachycardia. Circulation 103: 485-490, 2001.
Viitasalo M, Oikarinen L, Swan H, Väänänen H, Glatter K, Laitinen P, Kontula K, Barron HV, Toivonen L, Scheinman MM: Ambulatory electrocardiographic evidence of transmural dispersion of repolarization in patients with long-QT syndrome type 1 and 2. Circulation 106: 2473-2478, 2002.
Lehnart SE, Wehrens XH, Laitinen PJ, Reiken SR, Deng SX, Cheng Z, Landry DW, Kontula K, Swan H, Marks AR: Sudden death in familial polymorphic ventricular tachycardia associated with calcium channel release channel (ryanodine receptor) leak. Circulation 109: 3208-14, 2004.