Pertti Jääskeläinen

Publications (14)62.38 Total impact

• Article: Two founder mutations in the alpha-tropomyosin and the cardiac myosin-binding protein C genes are common causes of hypertrophic cardiomyopathy in the Finnish population.

  Pertti Jääskeläinen, Tiina Heliö, Katriina Aalto-Setälä, Maija Kaartinen, Erkki Ilveskoski, Liisa Hämäläinen, John Melin, Markku S Nieminen, Markku Laakso, Johanna Kuusisto, Helena Kervinen, Juha Mustonen, Jukka Juvonen, Mari Niemi, Paavo Uusimaa, Matti Huttunen, Matti Kotila, Mikko Pietilä
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  ABSTRACT: Background. Hypertrophic cardiomyopathy (HCM) is predominantly caused by a large number of various mutations in the genes encoding sarcomeric proteins. However, two prevalent founder mutations for HCM in the alpha-tropomyosin (TPM1-D175N) and myosin-binding protein C (MYBPC3-Q1061X) genes have previously been identified in eastern Finland. Objective. To assess the prevalence of these founder mutations in a large population of patients with HCM from all over Finland. Patients and methods. We screened for two founder mutations (TPM1-D175N and MYBPC3-Q1061X) in 306 unrelated Finnish patients with HCM from the regions covering a population of ∼4,000,000. Results. The TPM1-D175N mutation was found in 20 patients (6.5%) and the MYBPC3-Q1061X in 35 patients (11.4%). Altogether, the two mutations accounted for 17.9% of the HCM cases. In addition, 61 and 59 relatives of the probands were found to be carriers of TPM1-D175N and MYBPC3-Q1061X, respectively. The mutations showed regional clustering. TPM1-D175N was prevalent in central and western Finland, and MYBPC3-Q1061X in central and eastern Finland. Conclusion. The TPM1-D175N and MYBPC3-Q1061X mutations account for a substantial part of all HCM cases in the Finnish population, indicating that routine genetic screening of these mutations is warranted in Finnish patients with HCM.
  Annals of medicine 04/2012; · 3.52 Impact Factor
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  Available from: Anita Naukkarinen

  Article: Low-grade inflammation and the phenotypic expression of myocardial fibrosis in hypertrophic cardiomyopathy.

  Johanna Kuusisto, Vesa Kärjä, Petri Sipola, Ivana Kholová, Keijo Peuhkurinen, Pertti Jääskeläinen, Anita Naukkarinen, Seppo Ylä-Herttuala, Kari Punnonen, Markku Laakso
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  ABSTRACT: To investigate the role of inflammation in the phenotypic expression of myocardial fibrosis in hypertrophic cardiomyopathy (HCM). Clinical study. Kuopio University Hospital and University of Eastern Finland, Kuopio, Finland. Twenty-four patients with a single HCM-causing mutation D175N in the α-tropomyosin gene and 17 control subjects. Endomyocardial biopsy samples taken from the patients with HCM were compared with matched myocardial autopsy specimens. Levels of high-sensitivity C-reactive protein (hsCRP) and proinflammatory cytokines were measured in patients and controls. Myocardial late gadolinium enhancement (LGE) in cardiac MRI (CMRI) was detected. Endomyocardial samples in patients with HCM showed variable myocyte hypertrophy and size heterogeneity, myofibre disarray, fibrosis, inflammatory cell infiltration and nuclear factor kappa B (NF-κB) activation. Levels of hsCRP and interleukins (IL-1β, IL-1RA, IL-6, IL-10) were significantly higher in patients with HCM than in control subjects. In patients with HCM, there was a significant association between the degree of myocardial inflammatory cell infiltration, fibrosis in histopathological samples and myocardial LGE in CMRI. Levels of hsCRP were significantly associated with histopathological myocardial fibrosis. hsCRP, tumour necrosis factor α and IL-1RA levels had significant correlations with LGE in CMRI. A variable myocardial and systemic inflammatory response was demonstrated in patients with HCM attributable to an identified sarcometric mutation. Inflammatory response was associated with myocardial fibrosis, suggesting that myocardial fibrosis in HCM is an active process modified by an inflammatory response.
  Heart (British Cardiac Society) 03/2012; 98(13):1007-13. · 4.22 Impact Factor
• Article: Cardiac MRI assessed left ventricular hypertrophy in differentiating hypertensive heart disease from hypertrophic cardiomyopathy attributable to a sarcomeric gene mutation.

  Petri Sipola, Jarkko Magga, Minna Husso, Pertti Jääskeläinen, Keijo Peuhkurinen, Johanna Kuusisto
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  ABSTRACT: To evaluate the value of cardiac magnetic resonance imaging (CMRI)-assessed left ventricular hypertrophy (LVH) in differentiating between hypertensive heart disease and hypertrophic cardiomyopathy (HCM). 95 unselected subjects with mild-to-moderate hypertension, 24 patients with HCM attributable to the D175N mutation of the α-tropomyosin gene and 17 control subjects were studied by cine CMRI. Left ventricular (LV) quantitative and qualitative characteristics were evaluated. LV maximal end-diastolic wall thickness, wall thickness-to-LV volume ratio, end-diastolic septum thickness and septum-to-lateral wall thickness ratio were useful measures for differentiating between LVH due to hypertension and HCM. The most accurate measure for identifying patients with HCM was the LV maximal wall thickness ≥ 17 mm, with a sensitivity, specificity, negative predictive value, positive predictive value, and accuracy of 90%, 93%, 86%, 95% and 91%, respectively. LV maximal wall thickness in the anterior wall, or regional bulging in left ventricular wall was found only in patients with HCM. LV mass index was not discriminant between patients with HCM and those with LVH due to hypertension. LV maximal thickness measured by CMRI is the best anatomical parameter in differentiating between LVH due to mild-to-moderate hypertension and HCM attributable to a sarcomeric mutation. CMRI assessment of location and quality of LVH is also of value in differential diagnosis.
  European Radiology 01/2011; 21(7):1383-9. · 3.22 Impact Factor
• Article: Significance of plasma levels of N-terminal Pro-B-type natriuretic peptide on left ventricular remodeling in non-obstructive hypertrophic cardiomyopathy attributable to the Asp175Asn mutation in the alpha-tropomyosin gene.

  Jarkko Magga, Petri Sipola, Olli Vuolteenaho, Juha Risteli, Pertti Jääskeläinen, Keijo Peuhkurinen, Johanna Kuusisto
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  ABSTRACT: Hypertrophic cardiomyopathy (HC) is an inherited heart disease characterized by left ventricular (LV) remodeling. The present study was conducted to investigate the association of N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) levels with LV remodeling on magnetic resonance imaging and procollagen formation in 17 healthy controls and 24 patients with nonobstructive HC attributable to an identical Asp175Asn (aspartic acid to asparagine at codon 175) mutation in the alpha-tropomyosin gene. None of the patients had history of decompensated heart failure, and all patients had normal LV ejection fraction. Patients with HC had higher NT-pro-BNP levels compared with controls (median 60 pmol/L, range <40 to 359, vs <40 pmol/L; p <0.001), but 9 patients with HC had normal NT-pro-BNP levels (<40 pmol/L). In patients with HC, levels of NT-pro-BNP were correlated significantly with LV end-systolic volume index (r = 0.50, p <0.05), LV mass index (r = 0.47, p <0.05), proportion of hypokinetic segments (r = 0.50, p <0.05), and levels of serum aminoterminal propeptide of type III procollagen (r = 0.52, p <0.01). When patients with HC were divided into 3 groups on the basis of their NT-pro-BNP levels, there were statistically significant linear associations of LV end-systolic volume (test for linearity p = 0.034), LV mass index (p = 0.009), proportion of hypokinetic segments (p = 0.016), and levels of serum aminoterminal propeptide of type III procollagen (p = 0.020) with NT-pro-BNP levels over the 3 groups, suggesting a tight relation between LV remodeling and levels of NT-pro-BNP. In conclusion, in patients with nonobstructive HC attributable to an Asp175Asn mutation in the alpha-tropomyosin gene, elevated NT-pro-BNP levels are associated with incipient LV remodeling, suggesting that NT-pro-BNP could be used to diagnose insidious unfavorable LV remodeling in HC.
  The American Journal of Cardiology 04/2008; 101(8):1185-90. · 3.37 Impact Factor
• Article: Diastolic dysfunction without left ventricular hypertrophy is an early finding in children with hypertrophic cardiomyopathy-causing mutations in the beta-myosin heavy chain, alpha-tropomyosin, and myosin-binding protein C genes.

  Tuija Poutanen, Tero Tikanoja, Pertti Jääskeläinen, Eero Jokinen, Annuli Silvast, Markku Laakso, Johanna Kuusisto
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  ABSTRACT: We investigated the presence of left ventricular hypertrophy (LVH) and features of diastolic dysfunction in genotype-confirmed children from families with hypertrophic cardiomyopathy (HCM) and healthy control children. In subjects with HCM-causing mutations, LVH usually does not evolve until adolescence. Diastolic dysfunction has not been systematically evaluated in children carrying HCM-causing mutations. All children (aged 1.5-16.7 years) from 14 HCM families with identified disease-causing mutations (the Arg719Trp mutation in the beta-myosin heavy chain gene [MYH7], the Asp175Asn mutation in the alpha-tropomyosin gene [TPM1], the Gln1061X mutation in the myosin-binding protein C gene [MYBPC3], and the IVS5-2A-->C mutation in the MYBPC3 gene) and 53 matched control children were examined with electrocardiography and 2- and 3-dimensional echocardiography (2DE and 3DE). Natriuretic peptides were measured in children from HCM families and 67 control children. Of 53 children from HCM families, 27 (51%) had a disease-causing mutation (G+). G+ children had slightly thicker septum on 2DE compared with the control children (P = .004), but only 3 (11%) of 27 G+ children exceeded the 95th percentile values of the body surface area-adjusted maximal LV thickness of healthy children (the major echocardiographic criterion for HCM). However, prolonged isovolumetric relaxation time, increased left atrial volume on 3DE, or increased levels of NT-proANP, all features suggestive of diastolic dysfunction, were found in 14 (52%) of 27 G+ children. In children with HCM-causing mutations, signs of diastolic dysfunction are found in about half of the cases, as LVH is present only in small percentage of these children.
  American heart journal 04/2006; 151(3):725.e1-725.e9. · 4.65 Impact Factor
• Article: Cine MR imaging of myocardial contractile impairment in patients with hypertrophic cardiomyopathy attributable to Asp175Asn mutation in the alpha-tropomyosin gene.

  Petri Sipola, Kirsi Lauerma, Pertti Jääskeläinen, Markku Laakso, Keijo Peuhkurinen, Hannu Manninen, Hannu J Aronen, Johanna Kuusisto
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  ABSTRACT: To prospectively investigate the relationship between myocardial contractile impairment and left ventricular (LV) hypertrophy measured at cardiac magnetic resonance (MR) imaging in patients with hypertrophic cardiomyopathy (HCM) caused by the substitution of aspartic acid 175 with asparagine (ie, Asp175Asn mutation) in the alpha-tropomyosin gene (TPM1). The study protocol was approved by the hospital ethics committee, and all subjects gave written informed consent. LV mass, maximal LV wall thickness, and myocardial fractional thickening during systole were measured at cine MR imaging in 24 subjects (11 male, 13 female; mean age, 42 years; age range, 17-68 years) with the Asp175Asn mutation in TPM1 and in 17 healthy volunteers (eight men, nine women; mean age, 38 years; age range, 23-60 years). The proportion of hypokinetic LV segments was calculated as the number of LV segments with fractional thickening of less than 30% divided by the total number of segments measured. Anthropometric and biochemical correlates of LV hypertrophy were determined. Univariate and multiple linear regression analyses were used to investigate the association of the proportion of hypokinetic segments and other correlates of LV hypertrophy with LV mass and maximal wall thickness. The proportion of hypokinetic segments was higher in patients with HCM than in control subjects (37% +/- 20 [standard deviation] vs 12% +/- 12, P < .001). In stepwise multiple regression analysis, the proportion of hypokinetic segments accounted for 42% (P < .001); the LV end-diastolic volume, for 24% (P = .003); and male sex, for 10% (P = .014) of the variability in LV mass in patients with HCM. The proportion of hypokinetic LV segments, which accounted for 48% of the variability in LV maximal wall thickness (P < .001), was the only variable significantly associated with maximal wall thickness. The extent of myocardial contractile impairment is strongly and independently related to LV mass and maximal wall thickness in patients with HCM attributable to the Asp175Asn mutation in TPM1.
  Radiology 10/2005; 236(3):815-24. · 5.73 Impact Factor
• Article: Two novel mutations in the beta-myosin heavy chain gene associated with dilated cardiomyopathy.

  Satu Kärkkäinen, Tiina Heliö, Pertti Jääskeläinen, Raija Miettinen, Petri Tuomainen, Kari Ylitalo, Maija Kaartinen, Eeva Reissell, Lauri Toivonen, Markku S Nieminen, Johanna Kuusisto, Markku Laakso, Keijo Peuhkurinen
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  ABSTRACT: Dilated cardiomyopathy (DCM) is familial in approximately 20-35% of cases of idiopathic DCM. Several mutations in the different sarcomere protein genes have been reported to cause DCM. We wanted to investigate the role of sarcomere protein gene variants in Finnish DCM patients. We screened all coding exons of five sarcomere protein genes (beta-myosin heavy chain, alpha-tropomyosin, troponin C, troponin I and troponin T) in a well-characterized population of 52 DCM patients in Eastern Finland by the PCR-SSCP and sequencing method. Two novel mutations, Arg1053Gln and Arg1500Trp, in the beta-myosin heavy chain gene in two index patients were detected. The proband with the Arg1053Gln mutation had a dilated left ventricle and impaired systolic function, but other family members carrying this mutation presented with septal hypertrophy. It thus seems that the Arg1053Gln mutation is primarily a HCM mutation, which can also lead to DCM. The other mutation, Arg1500Trp, was associated with a typical DCM phenotype. The Arg1500Trp mutation carrier had only one family member alive, but she did not carry the mutation and, therefore, cosegregation of the mutation and the disease in this family could not be reliably verified. No disease-causing mutations were found in the other sarcomere protein genes. Two novel mutations in the beta-myosin heavy chain gene were detected in patients with DCM. Overall, mutations in the beta-myosin heavy chain gene seem to be relatively uncommon in Finnish DCM patients.
  European Journal of Heart Failure 01/2005; 6(7):861-8. · 4.90 Impact Factor
• Article: Genetics of hypertrophic cardiomyopathy in eastern Finland: few founder mutations with benign or intermediary phenotypes.

  Pertti Jääskeläinen, Raija Miettinen, Päivi Kärkkäinen, Lauri Toivonen, Markku Laakso, Johanna Kuusisto
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  ABSTRACT: Hypertrophic cardiomyopathy (HCM) is a genetically and clinically heterogeneous myocardial disease caused by mutations in genes encoding sarcomeric proteins. To assess the genetic background and phenotypic expression of HCM in eastern Finland, we screened 35 unrelated patients with HCM from the Kuopio University Hospital area for variants in 9 genes encoding sarcomeric proteins with the PCR-SSCP method. We herewith describe our previous findings in five sarcomeric genes and also report hitherto unpublished data on four additional sarcomeric genes. Mutations in the cardiac myosin-binding protein C gene (MYBPC3) were most frequent, accounting for 26% of cases. A novel mutation (Gln1061X) in this gene was the most common mutation, found in 6 of 35 families and accounting for 17% of all cases. Other novel mutations in MYBPC3 (IVS5-2A --> C, IVS14-13G --> A, and Ex25deltaLys) were found in one family each. A previously described alpha-tropomyosin (TPM1) mutation (Asp175Asn) was found in 11% of cases. Haplotype analysis suggested that the two most common variants (MYBPC3-Gln1061X and TPM1-Asp175Asn) were founder mutations. Only one mutation (Arg719Trp) in the beta-myosin heavy chain gene (MYH7) was found in one family, and no disease-causing mutations were found in the genes encoding alpha-actin, cardiac troponin I, T, C, or myosin essential and regulatory light chains. Altogether, the aforementioned 6 mutations found in MYBPC3, TPM1, and MYH7 accounted for 61% of familial and 40% of all HCM cases. The mutations were associated mostly with benign or intermediary phenotypes with only few HCM-related deaths. We conclude that the genetic profile of HCM in eastern Finland is unique, characterized by few founder mutations with benign or intermediary phenotypes.
  Annals of Medicine 02/2004; 36(1):23-32. · 3.52 Impact Factor
• Article: Cardiac adrenergic activity is associated with left ventricular hypertrophy in genetically homogeneous subjects with hypertrophic cardiomyopathy.

  Petri Sipola, Esko Vanninen, Hannu J Aronen, Kirsi Lauerma, Sakari Simula, Pertti Jääskeläinen, Markku Laakso, Keijo Peuhkurinen, Johanna Kuusisto, Jyrki T Kuikka
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  ABSTRACT: Hypertrophic cardiomyopathy (HCM) is a genetic disease caused by mutations in genes encoding sarcomeric proteins. However, other genetic and possibly also environmental factors modify the phenotypic expression of left ventricular (LV) hypertrophy. The present study investigated whether cardiac adrenergic activity affects the severity of LV hypertrophy in genetically identical patients with HCM. The study population consisted of 21 patients with HCM caused by the Asp175Asn substitution of the alpha-tropomyosin gene (TPM1-Asp175Asn) and 9 healthy volunteers. LV mass and segmental wall thickness were measured with MRI. Presynaptic cardiac adrenergic activity was measured with (123)I-metaiodobenzylguanidine (MIBG) SPECT. Global and segmental washouts of (123)I-MIBG were calculated. Global myocardial (123)I-MIBG washout was faster in patients with TPM1-Asp175Asn than in healthy volunteers (50% +/- 9% vs. 37% +/- 8%, P = 0.001). In linear regression analysis, global (123)I-MIBG washout was associated with the LV mass index and LV maximal wall thickness index in HCM patients (r = 0.512, P = 0.018, and r = 0.478, P = 0.028, respectively). The mean (123)I-MIBG washout was higher in LV segments >/= 15 mm thick than in LV segments < 15 mm thick (56 +/- 10 vs. 49% +/- 10%, P = 0.002). In patients with HCM sharing the same causal gene defect, the degree of LV hypertrophy is related to (123)I-MIBG washout, suggesting that cardiac adrenergic activity modifies phenotypic expression in HCM.
  Journal of Nuclear Medicine 04/2003; 44(4):487-93. · 6.38 Impact Factor
• Article: First-pass MR imaging in the assessment of perfusion impairment in patients with hypertrophic cardiomyopathy and the Asp175Asn mutation of the alpha-tropomyosin gene.

  Petri Sipola, Kirsi Lauerma, Minna Husso-Saastamoinen, Jyrki T Kuikka, Esko Vanninen, Tomi Laitinen, Hannu Manninen, Pekka Niemi, Keijo Peuhkurinen, Pertti Jääskeläinen, Markku Laakso, Johanna Kuusisto, Hannu J Aronen
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  ABSTRACT: To assess first-pass magnetic resonance (MR) imaging in the evaluation of perfusion impairment in a genetically homogeneous population of patients with hypertrophic cardiomyopathy (HCM) and the Asp175Asn mutation of the alpha-tropomyosin gene and to evaluate the association between hypertrophy and perfusion. Rest-stress first-pass MR imaging with gadopentetate dimeglumine was performed in 17 patients with HCM and the Asp175Asn substitution in the alpha-tropomyosin gene and in five control subjects. Global and segmental first-pass reserve index (FPR) measurements were derived from signal intensity versus time curves. Left ventricular (LV) wall thickness and LV mass index were measured on cine MR images. The Mann-Whitney test was used to evaluate the difference in FPR between the patient group and the control group. The Spearman correlation was used to evaluate the association between LV hypertrophy and FPR. Global FPR was significantly lower in the patients with HCM than in the control subjects (1.12 +/- 0.35 vs 1.80 +/- 0.58, P =.015). In patients with HCM, maximal LV wall thickness and LV mass index correlated negatively with global FPR (r = -0.723, P =.001 and r = -0.598, P =.011, respectively). At the regional level, segmental FPR correlated inversely with LV wall thickness (r = -0.389; P <.001) in patients with HCM. First-pass MR imaging facilitates global and regional evaluation of perfusion impairment in patients with HCM. The severity of perfusion impairment is associated with the degree of LV hypertrophy.
  Radiology 01/2003; 226(1):129-37. · 5.73 Impact Factor
• Article: No variants in the cardiac actin gene in Finnish patients with dilated or hypertrophic cardiomyopathy.

  Satu Kärkkäinen, Keijo Peuhkurinen, Pertti Jääskeläinen, Raija Miettinen, Päivi Kärkkäinen, Johanna Kuusisto, Markku Laakso
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  ABSTRACT: Dilated and hypertrophic cardiomyopathies are primary myocardial diseases that cause considerable morbidity and mortality. Although these cardiomyopathies are clinically heterogeneous, genetic factors play an important role in their etiology and pathogenesis. The defects in the cardiac actin (ACTC) gene can cause both cardiomyopathies. The aim of our study was to screen for variants in the ACTC gene in patients with dilated or hypertrophic cardiomyopathy from Eastern Finland. Altogether, 32 patients with dilated and 40 patients with hypertrophic cardiomyopathy were included in the study. Commonly approved diagnostic criteria were applied, and secondary cardiomyopathies were carefully excluded. All 6 exons of the ACTC gene were amplified with polymerase chain reaction and screened for variants with single-strand conformation polymorphism analysis. We did not find any new or previously reported variants. Our results indicate that defects in the ACTC gene do not explain dilated cardiomyopathy or hypertrophic cardiomyopathy in subjects from Eastern Finland and confirm earlier results that the ACTC gene does not play an important role in the genetics of dilated or hypertrophic cardiomyopathies.
  American heart journal 07/2002; 143(6):E6. · 4.65 Impact Factor
• Article: Mutations in the cardiac myosin-binding protein C gene are the predominant cause of familial hypertrophic cardiomyopathy in eastern Finland.

  Pertti Jääskeläinen, Johanna Kuusisto, Raija Miettinen, Päivi Kärkkäinen, Satu Kärkkäinen, Sami Heikkinen, Paula Peltola, Jussi Pihlajamäki, Ilkka Vauhkonen, Markku Laakso
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  ABSTRACT: Hypertrophic cardiomyopathy (HCM) is a genetic disorder characterized by cardiac hypertrophy caused by mutations in genes encoding sarcomere proteins. This study screened all patients with HCM from the Kuopio University Hospital region in eastern Finland for variants in the cardiac myosin-binding protein C gene ( MYBPC3). All 35 exons of MYBPC3 were screened by the single-strand conformation polymorphism method in 37 unrelated patients with HCM. In MYBPC3 we identified seven novel (Gln1061X, IVS5-2A-->C, IVS14-13G-->A, Ex25DeltaLys, Pro147Leu, Ser236Gly, and Arg1138His) and two previously reported (Arg326Gln, Val896Met) variants, all of which are predicted to affect the structure of the encoded protein. Four of the nine variants, a nonsense mutation Gln1061X, a splice acceptor mutation (IVS5-2A-->C), a novel substitution in intron 14 (IVS14-13G-->A), and a novel 3-bp deletion in exon 25 (Ex25DeltaLys) were concluded to be disease-causing mutations because they cosegregated with the HCM phenotype or were absent in more than 200 normal chromosomes, or both. The mutation Gln1061X was found most frequently, being present in 6 families (23 subjects) while the other three mutations were found in single families each. Haplotype analysis indicated a likely founder effect among the families carrying the Gln1061X mutation. We found four novel mutations in MYBPC3, accounting for approx. 38% of familial and 24% of all cases of HCM. In our previous and unpublished studies no more frequent cause of HCM has been found in genetic analyses of other eight sarcomeric proteins. Consequently MYBPC3 is the predominant gene for HCM in eastern Finland. In addition, several amino acid substitutions in MYBPC3 suspected to be not associated with HCM were identified, indicating that some of the missense variants found in MYBPC3 are possibly not disease-causing mutations.
  Journal of Molecular Medicine 07/2002; 80(7):412-22. · 4.67 Impact Factor
• Article: The Cardiac Troponin I Gene Is Not Associated with Hypertrophic Cardiomyopathy in Patients From Eastern Finland

  Pertti Jääskeläinen, Raija Miettinen, Karoliina Silvennoinen, Ilkka Vauhkonen, Markku Laakso, Johanna Kuusisto
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  ABSTRACT: Defects in seven genes encoding sarcomere proteins have been shown to cause hypertrophic cardiomyopathy. To date, only one study reporting defects in the cardiac troponin I gene associated with hypertrophic cardiomyopathy has been published, and the proportion of hypertrophic cardiomyopathy cases caused by defects in this gene is unknown. Therefore, the authors screened 37 unrelated Finnish patients with hypertrophic cardiomyopathy for variants in the cardiac troponin I gene. Exons 1–8 of the troponin I gene were screened with the polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) method. Five different variants (four intron variants and one silent exon variant) were found. Most variants were also present in control samples and none of the variants co-segregated with the disease in families. The results of the present study indicate that defects in the cardiac troponin I gene do not cause hypertrophic cardiomyopathy in patients from Eastern Finland.
  Journal of Molecular and Cellular Cardiology 12/1999; · 5.17 Impact Factor
• Article: Myocardial perfusion, oxidative metabolism, and free fatty acid uptake in patients with hypertrophic cardiomyopathy attributable to the Asp175Asn mutation in the alpha-tropomyosin gene: a positron emission tomography study.

  Helena Tuunanen, Johanna Kuusisto, Jyri Toikka, Pertti Jääskeläinen, Päivi Marjamäki, Keijo Peuhkurinen, Tapio Viljanen, Petri Sipola, Kira Q Stolen, Jarna Hannukainen, Pirjo Nuutila, Markku Laakso, Juhani Knuuti
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  ABSTRACT: The relationship between myocardial metabolic changes and the severity of left ventricular (LV) hypertrophy in patients with hypertrophic cardiomyopathy (HCM) is largely unknown. We characterized metabolic abnormalities in patients with a genetically identical cause for HCM but with variable LV hypertrophy. Eight patients with HCM attributable to the Asp175Asn mutation in the alpha-tropomyosin gene underwent myocardial perfusion, oxidative, and free fatty acid (FFA) metabolism measurements via positron emission tomography and oxygen 15-labeled water, carbon 11 acetate, and fluorine 14(R,S)-[18F] Fluoro-6-thia-heptadecanoic acid (18 FTHA). LV mass, work, and efficiency were assessed by echocardiography. Thirty-six healthy volunteers served as control subjects. Compared with control subjects, HCM patients had increased myocardial oxidative metabolism and FFA uptake (P < .05). However, in patients, LV mass was inversely related to global myocardial perfusion, oxidative metabolism, and FFA uptake (all P < .03), and regional wall thickness was inversely related to regional perfusion (P < .01), oxidative metabolism (P < .001), and FFA uptake (P < .01). Therefore patients with mild (LV mass less than median of 177 g) but not advanced LV hypertrophy were characterized by increased perfusion, oxidative metabolism, and LV efficiency as compared with control subjects (P < .05). In HCM attributable to the Asp175Asn mutation in the alpha-tropomyosin gene, myocardial oxidative metabolism and FFA metabolism are increased and inversely related to LV hypertrophy at both the whole heart and regional level. Increased metabolism and efficiency characterize patients with mild myocardial hypertrophy. These hypermetabolic alterations regress with advanced hypertrophy.
  Journal of Nuclear Cardiology 14(3):354-65. · 2.67 Impact Factor