Screening for BRCA1 and BRCA2 mutations in Eastern Finnish breast/ovarian cancer families.

Familial aggregation is thought to account for 5-10% of all breast cancer cases, and high penetrance breast and ovarian cancer susceptibility genes BRCA1 and BRCA2 explain < or =20% of these. Hundreds of mutations among breast/ovarian cancer families have been found in these two genes. The mutation spectrum and prevalence, however, varies widely among populations.

Type 2 diabetes whole-genome association study in four populations: the DiaGen consortium.

Type 2 diabetes (T2D) is a common, polygenic chronic disease with high heritability. The purpose of this whole-genome association study was to discover novel T2D-associated genes. We genotyped 500 familial cases and 497 controls with >300,000 HapMap-derived tagging single-nucleotide-polymorphism (SNP) markers.

A formative evaluation to develop a school health nursing early intervention model for adolescent substance use.

Objective: To improve an early intervention (EI) triggered by the Adolescents' Substance Use Measurement (ADSUME) as a method to prevent substance abuse among adolescents. We assessed how ADSUME and EI work in practice and how EI could be improved.

Design And Sample: School health nurses (n=10) tested ADSUME and EI on 14- to 18-year-old adolescents (n=228).

School health nurses and substance use among adolescents - towards individual identification and early intervention.

Adolescents' health is today threatened by the use of alcohol and other psychoactive substances. It is therefore important to develop interventions related to substance use in school health care. The aim of this study was to examine the empowering or risk background factors related to substance use among adolescents, and the ability of school nurses (PHN) to identify these factors and to provide needed individual early intervention.

Genome-wide linkage disequilibrium from 100,000 SNPs in the East Finland founder population.

Information about linkage disequilibrium (LD) is important in understanding the genome structure and has its applications in association studies. Here we present the first genome-wide LD study based on a founder population (East Finland). The LD data consist of 118 unrelated individuals and around 480,000 SNP pairs genotyped with the Affymetrix 100K genotyping assay.

Estrogen receptor beta gene variants are associated with increased risk of Alzheimer's disease in women.

We investigated the association of five intronic single-nucleotide polymorphism (SNP) at the estrogen receptor beta (ESR2) gene locus and the susceptibility of developing Alzheimer's disease (AD) in 387 subjects with clinically diagnosed probable AD and 467 cognitively normal individuals derived from eastern Finland. According to our results, variation in the ESR2 gene is associated with an increased risk of AD in women, whereas it does not contribute to the disease susceptibility in men. More specifically, in women, the allele T and the genotype T/T of two of the studied ESR2 gene SNPs (SNP2 and SNP3) were more frequent in AD women than in cognitively normal control women (P=0.

An autosome-wide scan for linkage disequilibrium-based association in sporadic breast cancer cases in eastern Finland: three candidate regions found.

Breast cancer is the most common of cancers among women in industrialized countries. Many of breast cancer risk factors are known, but the majority of the genetic background is still unknown. Linkage disequilibrium-based association is a powerful tool for mapping disease genes and is suitable for mapping complex traits in founder populations.

Haplotypic association of DDAH1 with susceptibility to pre-eclampsia.

Association between pre-eclampsia (PEE1) and the dimethylarginine dimethylaminohydrolase (DDAH) 1 and 2 genes, which play a role in the regulation of nitric oxide synthesis and release, was studied. In a case-control study design single nucleotide polymorphisms (SNPs) were determined at eight sites in the DDAH1 gene and at one site (Pro231Pro) in the DDAH2 gene from 132 women with pre-eclampsia and 112 healthy controls. Three SNPs in the DDAH1 gene were associated with pre-eclampsia, showing complete linkage disequilibrium with each other, but none of the associations in the allele or genotype data reached statistical significance in either of the genes after the correction for multiple testing.

Interleukin 1 alpha gene polymorphism as a susceptibility factor in Alzheimer's disease and its influence on the extent of histopathological hallmark lesions of Alzheimer's disease.

We investigated the association of the interleukin 1alpha (IL1A) (-889) C/T polymorphism with Alzheimer's disease (AD) and with the extent of AD histopathological lesions, the senile/neuritic plaques (SPs/NPs) and neurofibrillary tangles. We evaluated 98 neuropathologically confirmed AD patients and 240 controls as well as 146 clinically diagnosed AD patients and 278 controls but found no association of the IL1A C/T polymorphism with AD even after adjustment for the apolipoprotein E (APOE) genotype, gender or age. The extents of AD histopathological lesions were not influenced by the IL1A genotype except after exclusion of the APOE epsilon4 allele, when a trend towards more SPs/NPs was observed in AD patients with the IL1A C/C compared to patients with the T/T genotype.

Genome-wide linkage disequilibrium mapping of late-onset Alzheimer's disease in Finland.

Background: AD is a complex neurodegenerative disorder comprising several disease-associated chromosome loci. To find novel susceptibility genes for late-onset AD, a population-based genome-wide search using linkage disequilibrium (LD) mapping approach has been performed.

Method: Forty-seven patients with late-onset AD and 51 age-matched control subjects were carefully chosen from the same geographic area in eastern Finland, where the population is descended mainly from a small group of original founders.

Insertion-deletion polymorphism in the gene for angiotensin-converting enzyme is associated with obstetric cholestasis but not with preeclampsia.

Objective: Our purpose was to investigate the contribution of angiotensin-converting enzyme insertion-deletion polymorphism in the development of obstetric complications.

Study Design: In a retrospective case-control study, angiotensin-converting enzyme insertion-deletion polymorphism was investigated in a control group of healthy women (n = 115) and in a group of women diagnosed with preeclampsia (n = 133) and obstetric cholestasis (n = 57). Polymerase chain reaction detection of insertion-deletion polymorphism was used to determine the presence of the two angiotensin-converting enzyme alleles in the groups; the frequencies in the general population in our area are presented for comparison.

MPO and APOEepsilon4 polymorphisms interact to increase risk for AD in Finnish males.

Background: Myeloperoxidase (MPO) is present in senile plaques and surrounding reactive microglia, but not in normal brain parenchyma. MPO in plaques is highest in APOE epsilon4 carriers, suggesting a functional interaction. An MPO promoter polymorphism (-463G/A) linked to increased MPO expression has been associated with increased risk of AD.

Identification of a novel 4.6-kb genomic deletion in presenilin-1 gene which results in exclusion of exon 9 in a Finnish early onset Alzheimer's disease family: an Alu core sequence-stimulated recombination?

Mutations in the presenilin-1 (PS-1) gene have been shown to cause early onset Alzheimer's disease (EOAD) in an autosomal dominant manner. We have identified a novel 4.6-kb genomic deletion in the PS-1 gene in a Finnish EOAD family, which leads to an inframe exclusion of exon9 (delta9) from the mRNA transcript.

The leucine (7)-to-proline (7) polymorphism in the signal peptide of neuropeptide Y is not associated with Alzheimer's disease or the link apolipoprotein E.

Both apolipoprotein E varepsilon4 allele (APOE varepsilon4) and neuropeptide Y (NPY) Pro(7)-variant have been reported to be associated with higher serum levels of total and LDL cholesterol. Since APOE varepsilon4 allele is also a major risk factor for the development of Alzheimer's disease (AD) and the genetic polymorphism of NPY has not previously been studied in dementing disorders, we have examined whether a novel polymorphism in a signal peptide of NPY gene is associated with AD alone or in combination with APOE varepsilon4. A total of 125 sporadic AD cases and 110 control individuals from Finland were genotyped for APOE and NPY genes using the polymerase chain reaction and restriction enzyme analysis.