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Anna Rautanen

Publications and source records attributed to Anna Rautanen.

7 recordsLinked to original sources
PubMed2006

Associations of body size at birth with late-life cortisol concentrations and glucose tolerance are modified by haplotypes of the glucocorticoid receptor gene.

CONTEXT: Small body size at birth is associated with cardiovascular disease and type 2 diabetes in adult life. This link may be in part mediated by early-life programming of the hypothalamic-pituitary-adrenal axis (HPAA) function. OBJECTIVE: Our objective was to assess whether haplotypes of the glucocorticoid receptor (GR) gene modify this link. DESIGN AND PARTICIPANTS: We conducted a birth cohort study that included 437 men and women born in Helsinki, Finland, during 1924-1933, whose birth measurements were recorded. MAIN OUTCOME MEASURES: We studied how the oral glucose tolerance test and fasting plasma total and free cortisol concentrations and, in a subset of 162 women, a more detailed HPAA evaluation, are predicted by body size at birth and haplotypes of the GR locus. We also measured the haplotype-specific relative mRNA expression level for the haplotype of interest. RESULTS: One of the haplotypes was associated with lower birth weight and length and higher fasting plasma and mean 24-h salivary cortisol. Moreover, this haplotype modified the association of length at birth with adult phenotypes; in carriers, short length at birth was associated with increased fasting plasma cortisol, cortisol/corticosteroid-binding globulin ratio, impaired glucose tolerance or diabetes [1 cm decrease corresponded to 1.36-fold odds ratio; 95% confidence interval (CI), 1.09-1.70; P = 0.007], and higher 120-min glucose (5.8%; 95% CI, 2.5-9.1%; P = 0.0007), but no association was seen in noncarriers (P for interaction was 0.06, 0.01, 0.02, and 0.01, respectively). The mRNA expression level of this haplotype was 93.7% (95% CI, 90.5-96.8%; P = 2.2 x 10(-4)) of the expression level of the other haplotypes. CONCLUSIONS: A common GR haplotype may contribute to and modify the association of short length at birth with adult glucose tolerance and HPAA function by a mechanism that affects regulation of GR expression.

Aged↗
PubMed2006

An unfavorable combination of Factor V Leiden with age, weight, and blood group causes high risk of pregnancy-associated venous thrombosis: a population-based nested case-control study.

INTRODUCTION: Hereditary and acquired risk factors increase the risk for thrombosis among pregnant women. Few risk estimates are, however, well established. The aim of the present study was to assess risk for pregnancy-associated venous thrombosis of factor V Leiden (FVL), FII G20210A, FV A4070G, MTHFR C677T, TFPI C536T, PROC T38853G, FXIII V34L, blood group, age, and body mass index (BMI), and their interactions and public health impact. MATERIALS AND METHODS: Study design is a population-based nested case-control study of 100,000 consecutive pregnancies in Finland. Cases and controls were identified by combining national registers. Thirty four cases with objectively diagnosed venous thrombosis and 641 controls were studied. RESULTS: FVL (OR 11.6, 95% CI 3.6-33.6), age >35 vs. <25 (OR 6.3, 95% CI 1.7-23.1), and BMI >30 vs. <25 (OR 5.6, 95% CI 2.3-13.9) were associated with thrombosis. Overall absolute risk of a FVL carrier was 1 in 314. FVL interacted with age, BMI, and blood group. Population attributable risk proportion was 19% for FVL, 23% for age >35, 33% for BMI >25, and 35% for non-O blood group. Unexpectedly, the prevalence of FVL increased with age in controls. CONCLUSIONS: FVL appeared as a strong risk factor for pregnancy-associated venous thrombosis. Especially in elderly overweight mothers, FVL may cause a substantial thrombosis risk. Further studies are needed to confirm the increased prevalence of FVL in elderly mothers with normal pregnancies.

Adolescent↗
PubMed2006

Analysis of the mouse and human acyl-CoA thioesterase (ACOT) gene clusters shows that convergent, functional evolution results in a reduced number of human peroxisomal ACOTs.

The maintenance of cellular levels of free fatty acids and acyl-CoAs, the activated form of free fatty acids, is extremely important, as imbalances in lipid metabolism have serious consequences for human health. Acyl-coenzyme A (CoA) thioesterases (ACOTs) hydrolyze acyl-CoAs to the free fatty acid and CoASH, and thereby have the potential to regulate intracellular levels of these compounds. We previously identified and characterized a mouse ACOT gene cluster comprised of six genes that apparently arose by gene duplications encoding acyl-CoA thioesterases with localizations in cytosol (ACOT1), mitochondria (ACOT2), and peroxisomes (ACOT3-6). However, the corresponding human gene cluster contains only three genes (ACOT1, ACOT2, and ACOT4) coding for full-length thioesterase proteins, of which only one is peroxisomal (ACOT4). We therefore set out to characterize the human genes, and we show here that the human ACOT4 protein catalyzes the activities of three mouse peroxisomal ACOTs (ACOT3, 4, and 5), being active on succinyl-CoA and medium to long chain acyl-CoAs, while ACOT1 and ACOT2 carry out similar functions to the corresponding mouse genes. These data strongly suggest that the human ACOT4 gene has acquired the functions of three mouse genes by a functional convergent evolution that also provides an explanation for the unexpectedly low number of human genes.

Amino Acid Sequence↗
PubMed2005

Gene mapping with pooled samples on three genotyping platforms.

We have evaluated three genotyping techniques to detect allelic association between single nucleotide polymorphisms (SNPs) and disease loci by using pooled DNA samples. The use of DNA pools instead of individual samples saves considerably time, DNA quantity, and reagent costs. The methods that were compared were PCR-restriction fragment length polymorphism (PCR-RFLP), Single nucleotide primer extension, and chip-based mass spectrometry. As a model disease we studied an autosomal recessive disorder, congenital chloride diarrhea (CLD), caused by mutations in the human gene SLC26A3 on chromosome 7q31. Patient, carrier, and control pools were genotyped with eight SNP markers located within 10 cM around the target gene. Measured allele frequencies were consistent between the three platforms and we detected disease association with a cluster of several SNPs, the most significant being the marker located closest to the target gene (p=1.56 x 10(-16)). The largest source of error in pooled genotyping was shown to be the volumetric error in preparing the pools. The PCR-RFLP method was further evaluated by applying the pooling strategy to an ongoing multicenter-study. Measured allele frequencies of six polymorphisms agreed well with those measured individually and confirmed that multiple platforms are suitable for pooled genotyping.

Chromosome Mapping↗
PubMed2004

Characterization of a common susceptibility locus for asthma-related traits.

Susceptibility to asthma depends on variation at an unknown number of genetic loci. To identify susceptibility genes on chromosome 7p, we adopted a hierarchical genotyping design, leading to the identification of a 133-kilobase risk-conferring segment containing two genes. One of these coded for an orphan G protein-coupled receptor named GPRA (G protein-coupled receptor for asthma susceptibility), which showed distinct distribution of protein isoforms between bronchial biopsies from healthy and asthmatic individuals. In three cohorts from Finland and Canada, single nucleotide polymorphism-tagged haplotypes associated with high serum immunoglobulin E or asthma. The murine ortholog of GPRA was up-regulated in a mouse model of ovalbumin-induced inflammation. Together, these data implicate GPRA in the pathogenesis of atopy and asthma.

Algorithms↗
PubMed2004

The effects of the ACE gene insertion/deletion polymorphism on glucose tolerance and insulin secretion in elderly people are modified by birth weight.

The I allele of an insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme gene (ACE) appears to be protective against the complications of type 2 diabetes. Low birth weight, a marker of an adverse intrauterine environment, is associated with higher rates of type 2 diabetes. We examined whether the ACE I/D polymorphism could explain or modify the association between low birth weight and adulthood glucose tolerance. We measured plasma glucose and insulin concentrations after an oral glucose challenge in a group of 423 men and women, ages 65-75 yr, with measurements at birth recorded. The presence of the I allele was associated with shorter duration of gestation (P = 0.006) and, relative to gestational age, higher birth weight (P = 0.008) and length (P = 0.02). The I allele was associated with lower glucose at 120 min (P = 0.04) and a greater insulin response (P = 0.03 for insulin at 30 min and P = 0.06 for insulin area under the curve) to a standard oral glucose tolerance test. However, the associations between the ACE genotype and adulthood insulin secretion were only present in people with low birth weight (P for interaction birth weight * ACE genotype on insulin at 30 min = 0.003 and on insulin area under the curve = 0.05). The ACE I allele is associated with shorter duration of gestation and higher birth weight. The association between the presence of the ACE I allele and increased indices of adult insulin secretion is confined to subjects with low birth weight. We suggest that these findings reflect interactions between genotype and intrauterine environment with resulting changes in gene expression.

Birth Weight↗