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P J Tienari

Publications and source records attributed to P J Tienari.

At least 19 recordsLinked to original sources
PubMed2006

BDNF tagging polymorphisms and haplotype analysis in sporadic Parkinson's disease in diverse ethnic groups.

Experimental and clinical data suggest that genetic variations in brain-derived neurotrophic factor (BDNF) gene may affect risk for Parkinson's disease (PD). We performed a case-control association analysis of BDNF in three independent Caucasian cohorts (Greek, North American, and Finnish) of PD using eight tagging SNPs and five constructed haplotypes. No statistically significant differences in genotype and allele frequencies were found between cases and controls in all series. A relatively rare BDNF haplotype showed a trend towards association in the Greek (p=0.02) and the Finnish (p=0.03) series (this haplotype was not detected in the North American series). However, given the large number of comparisons these associations are considered non-significant. In conclusion, our results do not provide statistically significant evidence that common genetic variability in BDNF would associate with the risk for PD in the Caucasian populations studied here.

Aged↗
PubMed2006

Testing association between LRRK2 and Parkinson's disease and investigating linkage disequilibrium.

BACKGROUND: We and others recently identified the gene underlying PARK8 linked Parkinson's disease (PD). This gene, LRRK2, contains mutations that cause an autosomal dominant PD, including a mutation, G2019S, which is the most common PD causing mutation identified to date. Common genetic variability in genes that contain PD causing mutations has previously been implicated as a risk factor for typical sporadic disease. METHODS: We undertook a case-control association analysis of LRRK2 in two independent European PD cohorts using 31 tagging single nucleotide polymorphisms (tSNPs) and five potentially functional SNPs. To assess the structure of this locus in different populations, we have performed linkage disequilibrium (LD) analysis using these variants in a human diversity panel. RESULTS: We show that common genetic variability in LRRK2 is not associated with risk for PD in the European populations studied here. We also show inter-population variability in the strength of LD across this locus. CONCLUSIONS: To our knowledge this is the first comprehensive analysis of common variability within LRRK2 as a risk factor for PD.

Adult↗
PubMed2006

Association of tau haplotype-tagging polymorphisms with Parkinson's disease in diverse ethnic Parkinson's disease cohorts.

BACKGROUND: The overlap in the clinical and pathological features of tauopathies and synucleinopathies raises the possibility that the tau protein may be important in Parkinson's disease (PD) pathogenesis. Several MAPT polymorphisms that define the tau H1 haplotype have been investigated for an association with PD with conflicting results; however, two meta-analyses support an association between haplotype H1 and PD. METHODS: In this study, we recruited 508 patients and 611 healthy controls from Greek, Finnish and Taiwanese populations. We examined the possible genetic role of variation within MAPT in PD using haplotype-tagging single polymorphisms (SNPs) in these ethnically different PD populations. RESULTS: We identified a moderate association at SNP rs3785883 in the Greek cohort for both allele and genotype frequency (p = 0.01, p = 0.05, respectively) as well as for SNP rs7521 (genotype p = 0.02) and rs242557 (p = 0.01 genotypic, p = 0.04 allelic) in the Finnish population. There were no significant differences in genotype or allele distribution between cases and controls in the Taiwanese cohort. CONCLUSION: We failed to demonstrate a consistent association between the MAPT H1 haplotype (delineated by intron 9 ins/del) and PD in three ethnically diverse populations. However, the data presented here suggest that subhaplotypes of haplotype H1 may confer susceptibility to PD, and that either allelic heterogeneity or different haplotype composition explain the divergent haplotype results.

Adult↗
PubMed2005

Cerebral amyloid angiopathy in a 95+ cohort: complement activation and apolipoprotein E (ApoE) genotype.

There is growing evidence that in Alzheimer's disease (AD) amyloid beta-protein (Abeta) triggers a chronic inflammatory reaction in cerebral amyloid plaques, including complement proteins. Abeta also accumulates cerebrovascularly in age- and AD-associated cerebral amyloid angiopathy (CAA). We investigated complement proteins in CAA in a population-based series using histological and immunohistochemical staining methods. The 74 subjects, aged 95 years or more, had undergone clinical neurological examination and apolipoprotein E (ApoE) genotyping. The brains had been studied for AD post-mortem, allowing us to relate the histopathological findings to clinical and genetic conditions. CAA with congophilic amyloid was found in 36/74 individuals (48.6%). The vascular amyloid deposits immunoreacted with antibodies to Abeta and complements 3d (C3d) and 9 (C9). The positivity in complement stains increased with growing severity of CAA (P = 0.001). The presence of CAA associated with ApoE epsilon4 (P = 0.0005) and overrepresentation of epsilon4 among those with moderate or severe vs. mild CAA (P = 0.03) was demonstrated. The presence of CAA associated with dementia (P = 0.01), which was contributed by both epsilon4+ (P = 0.02) and epsilon4- (P = 0.06) subjects. Our study shows that complement proteins are deposited in the affected vessels in Abeta-associated CAA. They may solely represent the cerebral Abeta- burden associated to inflammatory stimuli, or signal a contribution in the clearance of cerebral Abeta, thereby contributing to the events associated with evolution of clinical dementia. Our results demonstrate a strong association between CAA and ApoE epsilon4 as well as dementia and suggest that the contribution of CAA to dementia is largely independent of ApoE epsilon4.

Aged, 80 and over↗
PubMed2005

How useful is [123I]beta-CIT SPECT in clinical practice?

OBJECTIVE: To assess the accuracy and clinical usefulness of [(123)I]beta-CIT (2beta-carbomethoxy-3beta-(4-iodophenyl)tropane) SPECT in the differential diagnosis of Parkinson's disease. SUBJECTS: 185 consecutive patients with symptoms of movement disorder were studied. The diagnoses were Parkinson's disease (92), essential tremor (16), vascular parkinsonism (15), various Parkinson plus syndromes (P+) (12), dementia with Lewy bodies (DLB) (5), dystonia (5), drug induced movement disorder (12), and other diagnoses (8). A reference group (psychogenic parkinsonism) comprised 20 subjects with complaints suggesting extrapyramidal disease but with no unequivocal signs on clinical examination and no abnormalities on brain imaging. RESULTS: beta-CIT uptake was significantly lower in the whole striatum as well as separately in the putamen and in the caudate nucleus in Parkinson's disease than in the reference group or in drug induced movement disorder, essential tremor, or dystonia. The uptake of beta-CIT in the vascular parkinsonism group was heterogeneous and mean beta-CIT uptake fell between the reference group and the Parkinson's disease group. In the P+ and DLB groups the striatal uptake ratios overlapped those of the Parkinson's disease group. CONCLUSIONS: [(123)I]beta-CIT SPECT may not be as useful a tool in the clinical differential diagnosis of Parkinson's disease as was previously believed, but it was 100% sensitive and specific for the diagnosis in younger patients (age <55 years). In older patients (age >55 years) specificity was substantially lower (68.5%). This differential specificity reflected the different distribution of differential diagnostic disorders (P+, DLB, vascular parkinsonism) in the older and younger age groups.

Age Factors↗
PubMed2004

Confirmation of the protective effect of iNOS in an independent cohort of Parkinson disease.

Nitric oxide is a biologic messenger molecule involved in a diverse range of physiologic processes. An exon 22 inducible nitric oxide synthase genotype has recently been reported to be protective against Parkinson disease in a European cohort. The authors confirm the protective effect of this genotype (OR = 0.5, 95% CI 0.27 to 0.93) in an independent Finnish case-control series.

Adult↗
PubMed2004

A two-stage study on multiple sclerosis susceptibility and chromosome 2q33.

We have performed a two-stage study to analyse the association of polymorphism on chromosome 2q33 with multiple sclerosis (MS). In all, 17 markers were analysed in stage-1 in 134 Finnish MS families and the observed associations were tested in stage-2 in 186 MS families. We did not find previously reported allelic or haplotype associations with CTLA4. We obtained a weak signal of two distinct predisposing genes, one proximal the other distal of CTLA4. The putative proximal gene was associated with the marker rs3977 in families lacking HLA-DR2 (P=0.02 and 0.02) and the other distal gene was associated with D2S1271 in families from a high-risk region in western Finland (P=0.02 and 0.01). Based on the >3 cM distance and the lack of linkage disequilibrium between these loci, we conclude that the two association signals are independent. Our results provide preliminary evidence for two distinct MS susceptibility genes on 2q33 outside of CTLA4.

Antigens, CD↗
PubMed2003

Assessment of a DJ-1 (PARK7) polymorphism in Finnish PD.

Mutations in DJ-1 are a cause of autosomal recessive parkinsonism. Polymorphism of genes implicated in hereditary forms of parkinsonism may be a predisposing factor in sporadic Parkinson's disease (PD). The authors analyzed whether a polymorphism (g.168_185del) within exon 1 of DJ-1 contributes to the risk of sporadic PD in a Finnish case-control series. This gene does not play a major role in the genetic predisposition to PD in this population.

Adult↗
PubMed2003

Linkage disequilibrium between the MBP tetranucleotide repeat and multiple sclerosis is restricted to a geographically defined subpopulation in Finland.

We have previously found evidence for linkage as well as allelic and haplotype association between the myelin basic protein (MBP) gene and multiple sclerosis (MS). These findings have, however, not been reproduced in other populations. Here, we have analyzed association between MBP and MS in a new set of 349 Finnish triad families. Families with a parent born in the Southern Ostrobothnian region in western Finland (Bothnia families, n=98) were analyzed as a separate group since our previous studies included a high proportion of patients and families from this high-incidence region. Other families (n=251) were collected at five hospitals in southern, eastern, and northern Finland. The MBP short tandem repeat was genotyped, and haplotype patterns were verified by sequencing. In the Bothnia families, the previously detected associations with the 1.27 kb allele and haplotype 1.27-B10 were confirmed (P=0.01 and 0.02, respectively), whereas in the other families there was not even a trend toward association. These results demonstrate a geographic/genealogical restriction in the association between MS and the MBP short tandem repeat, highlight the importance of genealogical information in genetic studies of complex traits, and may provide an explanation why the association has not been found in many other populations.

Alleles↗
PubMed2003

Peptidylarginine deiminase, the arginine to citrulline converting enzyme, is frequently recognized by sera of patients with rheumatoid arthritis, systemic lupus erythematosus and primary Sjögren syndrome.

OBJECTIVE: Antibodies to citrulline-containing epitopes of filaggrin are highly specific for rheumatoid arthritis (RA). We studied whether the enzyme peptidylarginine deiminase (PAD), responsible for the post-translational modification of peptide-bound arginine residues to citrulline, constitutes an antigen for patients with RA. METHODS: IgG antibodies to PAD were measured by enzyme-linked immunosorbent assay (ELISA) in sera from patients with RA, systemic lupus erythematosus (SLE), primary Sjögren syndrome (pSS), multiple sclerosis (MS) and healthy controls. RESULTS: Compared to healthy controls, raised levels of IgG antibodies to PAD were found in 50 of 57 recent-onset RA patients (88%) and in 40 (70%) of the same 57 patients 3 years later (p<0.0001 for both comparisons). Eleven of 51 (22%) patients with RA of long duration, 19/43 (44%) patients with SLE and 16/19 (84%) patients with pSS, but none of 20 patients with MS, had elevated anti-PAD levels. CONCLUSION: The arginine-citrulline converting enzyme PAD was recognized as a new antigen against which patients with inflammatory rheumatic diseases frequently show IgG class antibodies.

Adult↗
PubMed2003

Multiple sclerosis in Finland: incidence trends and differences in relapsing remitting and primary progressive disease courses.

OBJECTIVE: To compare the secular trends and geographical differences in the incidence of relapsing-remitting (RRMS) and primary progressive multiple sclerosis (PPMS) in Finland, and to draw inferences about aetiological differences between the two forms of the disease. METHODS: New multiple sclerosis cases in southern Uusimaa and the western districts Vaasa and Seinäjoki of Finland in 1979-1993 were verified from hospital records and classified into RRMS and PPMS. Patients met the Poser criteria for definite multiple sclerosis or otherwise satisfied the criteria for PPMS. Disease course was categorised by the same neurologist. Crude and age adjusted incidence in 1979-1993 was estimated. RESULTS: During 1979-1993 the age adjusted incidence was 5.1 per 100 000 person-years in Uusimaa, 5.2 in Vaasa, and 11.6 in Seinäjoki. The rates in Uusimaa remained stable, while a decrease occurred in Vaasa and an increase in Seinäjoki. Between 1979-86 and 1987-93 the incidence of PPMS increased in Seinäjoki from 2.6 to 3.7 per 10(5) and decreased in Vaasa from 1.9 to 0.2 per 10(5); the trends were similar for RRMS. CONCLUSIONS: There are significant differences in secular trends for multiple sclerosis incidence in Finland by geographical area, but these are similar for PPMS and RRMS. The recent changes point to locally acting environmental factors. The parallel incidence trends for RRMS and PPMS suggest similar environmental triggers for the two clinical presentations of multiple sclerosis.

Adolescent↗
PubMed2002

Apolipoprotein E (APOE), PARKIN and catechol-O-methyltransferase (COMT) genes and susceptibility to sporadic Parkinson's disease in Finland.

Recent studies have demonstrated that genetic factors modify susceptibility to sporadic Parkinson's disease (PD). So far the results of candidate gene studies have been conflicting. It has been suggested that polymorphisms in apolipoprotein E (APOE), PARKIN and catechol-O-methyltransferase (COMT) genes might increase the risk of PD. We studied 147 Finnish non-demented patients with sporadic PD and 137 controls. APOE epsilon allele and genotype frequencies in PD patients did not differ significantly from controls. Three single nucleotide polymorphisms of the PARKIN gene and an intronic and an exonic (Val158Met) polymorphism of the COMT gene were studied. None of these polymorphisms showed association with PD in our series. In contrast to reports in oriental populations, our results do not support a major role of APOE, PARKIN and COMT polymorphisms in PD susceptibility in the Finnish population.

Adult↗
PubMed2002

Contribution of APOE promoter polymorphisms to Alzheimer's disease risk.

OBJECTIVE: To determine whether the effects of APOE promoter polymorphisms on AD are independent of the APOE-epsilon4 allele. BACKGROUND: Recently, the -491 A-->T and -219 G-->T polymorphisms located in the APOE promoter have been suggested to be risk factors for AD. However, the effects of these polymorphisms have not always been reproduced in case-control studies, possibly because of the strong linkage disequilibrium existing at this locus or the characteristics of the populations studied. METHODS: Data collection was performed from six independent samples (1,732 patients with AD and 1,926 control subjects) genotyped for APOE exon 4 and the two APOE promoter polymorphisms. The risks associated with the APOE polymorphisms for developing AD were estimated using logistic regression procedures and calculation of odds ratios with 95% CI adjusted by age, sex, and collection center. Independence of the APOE promoter polymorphisms was tested by stratification for APOE-epsilon4 and tertile design was used for age stratification. RESULTS: The independence of the -491 AA genotype was observed in the whole sample whereas the independence of the -219 TT genotype was observed only in the oldest population. CONCLUSION: The -491 and -219 APOE promoter polymorphisms incur risk for AD in addition to risk associated with the APOE-epsilon4 allele, with age accentuating the effect of the -219 TT genotype. Because these polymorphisms appear to influence apoE levels, these results suggest that APOE expression is an important determinant of AD pathogenesis.

Aged↗
PubMed2002

Chromosome 19q13 and multiple sclerosis susceptibility in Finland: a linkage and two-stage association study.

Several studies have previously provided some albeit weak evidence for linkage or association between chromosome 19q13 and multiple sclerosis (MS) susceptibility. We performed a two-stage association analysis with 19 markers spanning 7 Mb/5.5 cM of 19q13. In stage 1 analysis (135 MS families) allelic and haplotypic associations were found with markers within or close to the ApoE-ApoC subregion. These observations were taken as a hypothesis, which was tested in stage 2 in 125 families. However, none of the initial associations were replicated suggesting that they were most likely due to chance. Linkage analysis was performed in 27 Finnish multiplex families using 10 microsatellites spanning 23 Mb/24 cM of 19q13. DNA was available from 72 MS patients and 150 unaffected relatives. Parametric and non-parametric linkage analyses did not provide evidence for linkage when all families were tested. After stratifying the families according to HLA-DR15 there was weak evidence for linkage to the 19q13.1 subregion in DR15 negative families (LOD(max)=1.8). Taken together these results do not support a major role of chromosome 19q13.2-q13.3 in MS susceptibility among Finnish MS patients, whereas conclusions on the 19q13.1 subregion are less clear and this region requires further study.

Adolescent↗
PubMed2002

Survival of multiple sclerosis in Finland between 1964 and 1993.

The long-term survival of multiple sclerosis (MS) was studied during 1964-1993 in a cohort of 1614 patents in Finland. Survival to death from the initial MS symptoms was analysed by the life-table method, separately for MS related and all causes of deaths. Survival at 40 years was 64% for MS deaths and 53% for all deaths. Higher proportions of violent deaths and neoplasms were observed among MS patients as compared to the general population, whereas the proportion of cardiovascular causes of death was low. MS-related causes accounted for 70% of the recorded 219 deaths. Favourable survival in MS was associated with relapsing-remitting disease course, age at onset below 30 years and optic neuritis or other sensory symptoms at presentation. We were unable to show any significant effect due to calendar time of diagnosis or gender, as the risk of men was similar (risk ratio [RR] = 1.1, confidence interval [CI] 0.8-1.6) as compared to women.

Adult↗
PubMed2001

Increasing prevalence of multiple sclerosis in Finland.

OBJECTIVES: To follow-up the prevalence trends of MS from 1983 to 1993 in western and southern Finland. MS epidemiology has been previously followed from 1964 to 1978 in these regions. The updated prevalences were correlated with incidence trends in the same period. METHODS: Age-adjusted and age-specific MS prevalence rates were calculated for cases classified by Poser's criteria. RESULTS: In the western health-care districts, Seinäjoki and Vaasa, prevalences in 1993 were 202/10(5) and 111/10(5). In the southern district Uusimaa the respective figure was 108/10(5). In Seinäjoki a significant 1.7-fold increase was found in 1993 as compared to 1983, mainly due to increased incidence. In Uusimaa a significant 1.2-fold increase in prevalence was found in the presence of stable incidence. In Vaasa prevalence was stable, although incidence was declining. CONCLUSION: The prevalence of MS is increasing in Seinäjoki and Uusimaa but not in Vaasa. Both the prevalence and incidence in Seinäjoki are now among the highest reported.

Adolescent↗
PubMed2001

Association of lipoprotein lipase Ser447Ter polymorphism with brain infarction: a population-based neuropathological study.

BACKGROUND: Variants of the lipoprotein lipase (LPL) gene have been shown to influence serum lipid levels, risk of coronary heart disease and, as found recently, risk of clinical ischaemic cerebrovascular disease. Here we tested for an association between brain infarction and two common polymorphisms of the LPL gene, Ser447Ter and Asn291 Ser. METHOD: To avoid ascertainment and selection bias involved in many association studies, we compared the distribution of these polymorphisms in neuropathologically verified patients (n = 119) vs controls (n = 133) derived from a prospective, population-based study (the Vantaa 85+ study). RESULTS: The LPL Ter447 variant was negatively associated with neuropathologically verified brain infarcts (P = 0.006), and even more strongly with small brain infarcts (P = 0.004). In addition, we found that the Ter447 variant was associated with higher serum HDL chblesterol (P = 0.004) and lower triglyceride levels (P= 0.003), and that it was negatively associated with pathologically verified severe coronary artery disease (P=0.001) in the Vantaa 85+ study sample. The Asn291Ser polymorphism was not significantly associated with brain infarction. CONCLUSION: The Ter447 variant of LPL is associated with decreased risk of brain infarction and coronary artery disease in our very elderly population.

Aged↗