Biomedical subjects

Bettina Fischer

Publications and source records attributed to Bettina Fischer.

9 recordsLinked to original sources

PubMed2006

SimArray: a user-friendly and user-configurable microarray design tool.

BACKGROUND: Microarrays were first developed to assess gene expression but are now also used to map protein-binding sites and to assess allelic variation between individuals. Regardless of the intended application, efficient production and appropriate array design are key determinants of experimental success. Inefficient production can make larger-scale studies prohibitively expensive, whereas poor array design makes normalisation and data analysis problematic. RESULTS: We have developed a user-friendly tool, SimArray, which generates a randomised spot layout, computes a maximum meta-grid area, and estimates the print time, in response to user-specified design decisions. Selected parameters include: the number of probes to be printed; the microtitre plate format; the printing pin configuration, and the achievable spot density. SimArray is compatible with all current robotic spotters that employ 96-, 384- or 1536-well microtitre plates, and can be configured to reflect most production environments. Print time and maximum meta-grid area estimates facilitate evaluation of each array design for its suitability. Randomisation of the spot layout facilitates correction of systematic biases by normalisation. CONCLUSION: SimArray is intended to help both established researchers and those new to the microarray field to develop microarray designs with randomised spot layouts that are compatible with their specific production environment. SimArray is an open-source program and is available from http://www.flychip.org.uk/SimArray/.

Documentation↗

PubMed2005

Association of common variation in the PPARA gene with incident myocardial infarction in individuals with type 2 diabetes: a Go-DARTS study.

BACKGROUND: Common variants of the PPARA gene have been found to associate with ischaemic heart disease in non diabetic men. The L162V variant was found to be protective while the C2528G variant increased risk. L162V has also been associated with altered lipid measures. We therefore sought to determine the effect of PPARA gene variation on susceptibility to myocardial infarction in patients with type 2 diabetes. 1810 subjects with type 2 diabetes from the prospective Go-DARTS study were genotyped for the L162V and C2528G variants in the PPARA gene and the association of the variants with incident non-fatal myocardial infarction was examined. Cox's proportional hazards was used to interrogate time to event from recruitment, and linear regression for analysing association of genotype with quantitative clinical traits. RESULTS: The V162 allele was associated with decreased risk of non-fatal myocardial infarction (HR = 0.31, 95%CI 0.10-0.93 p = 0.037) whereas the C2528 allele was associated with increased risk (HR = 2.77 95%CI 1.34-5.75 p = 0.006). Similarly V162 was associated with a later mean age of diagnosis with type 2 diabetes and C2582 an earlier age of diagnosis. C2528 was also associated with increased total cholesterol and LDL cholesterol, which did not account for the observed increased risk. Haplotype analysis demonstrated that when both rare variants occurred on the same haplotype the effect of each was abrogated. CONCLUSION: Genetic variation at the PPARA locus is important in determining cardiovascular risk in both male and female patients with diabetes. This genotype associated risk appears to be independent of the effect of these genotypes on lipid profiles and age of diagnosis with diabetes.

Journal Article↗

PubMed2005

Robotic spotting of cDNA and oligonucleotide microarrays.

DNA microarrays are a uniquely efficient method for simultaneously assessing the expression levels of thousands of genes. Owing to their flexibility and value, mechanically spotted microarrays remain the most popular platform. Here, we review recent technological advances with a focus on spotted arrays. Robotic spotting still poses numerous technical challenges. To reduce artefacts, many laboratories have recently investigated ways of improving the spotting process. We compare alternative options and discuss implications for next-generation systems. Together with modern approaches to data analysis, such developments bring greatly improved reliability to individual microarray experiments. Advancing towards the ultimate goal of delivering calibrated, truly quantitative gene-expression measurements on a genomic scale, microarray technology remains at the forefront of post-genomic systems biology.

DNA Probes↗

PubMed2004

Cardiovascular risk in type 2 diabetes is associated with variation at the PPARG locus: a Go-DARTS study.

OBJECTIVE: The Pro12Ala polymorphism of PPARG modulates risk of developing type 2 diabetes. The Ala allele has also been associated with a reduced risk of cardiovascular events. We have shown previously that the linked T allele of the C1431T polymorphism influences Ala12-associated diabetes risk and that the 2 polymorphisms have opposing associations with body weight. We therefore investigated the association of these 2 variants with cardiovascular events in people with type 2 diabetes. METHODS AND RESULTS: We performed a cohort study of 2016 individuals and used Cox proportional hazards to analyze risk of myocardial infarction or death by PPARG Pro12Ala and C1431T genotypes, adjusting for age, sex, and smoking status. In individuals enrolled <70 years of age, the hazard for a first nonfatal event associated with the Ala12 allele was 0.21 (CI, 0.06 to 0.69; P=0.01) and the T1431 allele 9.9 (CI, 1.90 to 51.29; P=0.007). These opposing associations remained significant after correction for other conventional risk factors. The T1431 allele was also associated with all-cause mortality. CONCLUSIONS: This study confirms the association of the Ala12 allele with reduced risk of myocardial infarction in a type 2 diabetic population and demonstrates that the T allele independently associates with an increased risk.

Age Factors↗

PubMed2004

Hereditary and acquired angioedema: problems and progress: proceedings of the third C1 esterase inhibitor deficiency workshop and beyond.

Hereditary angioedema (HAE), a rare but life-threatening condition, manifests as acute attacks of facial, laryngeal, genital, or peripheral swelling or abdominal pain secondary to intra-abdominal edema. Resulting from mutations affecting C1 esterase inhibitor (C1-INH), inhibitor of the first complement system component, attacks are not histamine-mediated and do not respond to antihistamines or corticosteroids. Low awareness and resemblance to other disorders often delay diagnosis; despite availability of C1-INH replacement in some countries, no approved, safe acute attack therapy exists in the United States. The biennial C1 Esterase Inhibitor Deficiency Workshops resulted from a European initiative for better knowledge and treatment of HAE and related diseases. This supplement contains work presented at the third workshop and expanded content toward a definitive picture of angioedema in the absence of allergy. Most notably, it includes cumulative genetic investigations; multinational laboratory diagnosis recommendations; current pathogenesis hypotheses; suggested prophylaxis and acute attack treatment, including home treatment; future treatment options; and analysis of patient subpopulations, including pediatric patients and patients whose angioedema worsened during pregnancy or hormone administration. Causes and management of acquired angioedema and a new type of angioedema with normal C1-INH are also discussed. Collaborative patient and physician efforts, crucial in rare diseases, are emphasized. This supplement seeks to raise awareness and aid diagnosis of HAE, optimize treatment for all patients, and provide a platform for further research in this rare, partially understood disorder.

Angioedema↗

PubMed2004

Disco clothing, female sexual motivation, and relationship status: is she dressed to impress?

The relationship between a female's clothing choice, sexual motivation, hormone levels, and partnership status (single or not single, partner present or not present) was analyzed in 351 females attending Austrian discotheques. We digitally analyzed clothing choice to determine the amount of skin display, sheerness, and clothing tightness. Participants self-reported sexual motivation, and we assessed estradiol and testosterone levels through saliva sampling. Results show that females are aware of the social signal function of their clothing and that they in some cases alter their clothing style to match their courtship motivation. In particular, sheer clothing -although rare in the study- positively correlated with the motivation for sex. Hormone levels influenced clothing choice in many groups, with testosterone levels correlating positively with physique display. In females who had a partner but were at the disco unaccompanied by the partner, estradiol levels correlated positively with skin display and clothing tightness. Significant differences were not found, however, for clothing choice across the partnership-status groups.

Adult↗

PubMed2003

Male preponderance in early diagnosed type 2 diabetes is associated with the ARE insertion/deletion polymorphism in the PPP1R3A locus.

BACKGROUND: The ARE insertion/deletion polymorphism of PPP1R3A has been associated with variation in glycaemic parameters and prevalence of diabetes. We have investigated its role in age of diagnosis, body weight and glycaemic control in 1,950 individuals with type 2 diabetes in Tayside, Scotland, and compared the ARE2 allele frequencies with 1,014 local schoolchildren. RESULTS: Men homozygous for the rarer allele (ARE2) were younger at diagnosis than ARE1 homozygotes (p = 0.008). Conversely, women ARE2 homozygotes were diagnosed later than ARE1 homozygotes (p = 0.036). Thus, men possessing the rarer (ARE2) allele were diagnosed with type 2 diabetes earlier than women (p < 0.000001). In contrast, there was no difference in age of diagnosis by gender in those individuals carrying only the common ARE1 variant. Furthermore, although there was no difference in the frequency between the children and the type 2 diabetic population overall, marked differences in allele frequencies were noted by gender and age-of diagnosis. The ARE2 allele frequency in early diagnosed males (diagnosed earlier than the first quartile of the overall ages at diagnosis) was higher than that found in both later diagnosed males and healthy children (p = 0.021 and p = 0.03 respectively). By contrast, the frequency in early diagnosed females was significantly lower than later diagnosed females and that found in children (p = 0.021 and p = 0.037). Comparison of the male to female ratios at different ages-diagnosed confirms a known phenomenon that men are much more prone to early type 2 diabetes than women. When this feature was examined by the common ARE 1/1 genotype we found that the male to female ratio remained at unity with all ages of diagnosis, however, carriers of the ARE2 variant displayed a marked preponderance of early male diagnosis (p = 0.003). CONCLUSION: The ARE2 allele of PPP1R3A is associated with a male preponderance to early diagnosed type 2 diabetes. Susceptibility to type 2 diabetes in later life is not modulated by the ARE2 allele in either sex.

AT Rich Sequence↗

PubMed2003

Recurrent episodes of skin angioedema and severe attacks of abdominal pain induced by oral contraceptives or hormone replacement therapy.

PURPOSE: Recurrent angioedema, characterized by skin swelling, colicky attacks of abdominal pain, and life-threatening laryngeal edema, can be either hereditary or acquired. According to anecdotal reports, it may be associated with use of oral contraceptives and hormone replacement therapy. We investigated potential interactions between these medications and various types of recurrent angioedema in a large cohort of women. METHODS: Women with recurrent angioedema (n = 516) underwent a thorough medical evaluation. They were then classified by type of angioedema, using standard criteria. RESULTS: Of the 516 women, 228 (44%) had used oral contraceptives or hormone replacement therapy, including 103 (45%) with urticaria-related angioedema, 50 (22%) with idiopathic angioedema, 39 (17%) with hereditary angioedema type III, 32 (14%) with hereditary angioedema type I, and 4 (2%) with angioedema induced by angiotensin-converting enzyme inhibitors. Oral contraceptives or hormone replacement therapy led to angioedema attacks in 46 women (20%), including 20 (63%) of the women with hereditary angioedema type I, 24 (62%) of those with hereditary angioedema type III, and 2 (4%) of those with idiopathic angioedema. These 46 women included 26 in whom symptoms occurred for the first time after use of these medications and 20 in whom pre-existing recurrent angioedema worsened considerably. CONCLUSION: Oral contraceptives or hormone replacement therapy can either induce or exacerbate symptoms of hereditary angioedema type I or type III, or idiopathic angioedema. However, many women with these diseases tolerate these medications without having any effects on their angioedema.

Abdominal Pain↗

PubMed2002

Haplotype analysis of the PPARgamma Pro12Ala and C1431T variants reveals opposing associations with body weight.

BACKGROUND: Variation at the PPARG locus may influence susceptibility to type 2 diabetes and related traits. The Pro12Ala polymorphism may modulate receptor activity and is associated with protection from type 2 diabetes. However, there have been inconsistent reports of its association with obesity. The silent C1431T polymorphism has not been as extensively studied, but the rare T allele has also been inconsistently linked to increases in weight. Both rare alleles are in linkage disequilibrium and the independent associations of these two polymorphisms have not been addressed. RESULTS: We have genotyped a large population with type 2 diabetes (n = 1107), two populations of non-diabetics from Glasgow (n = 186) and Dundee (n = 254) and also a healthy group undergoing physical training (n = 148) and investigated the association of genotype with body mass index. This analysis has demonstrated that the Ala12 and T1431 alleles are present together in approximately 70% of the carriers. By considering the other 30% of individuals with haplotypes that only carry one of these polymorphisms, we have demonstrated that the Ala12 allele is consistently associated with a lower BMI, whilst the T1431 allele is consistently associated with higher BMI. CONCLUSION: This study has therefore revealed an opposing interaction of these polymorphisms, which may help to explain previous inconsistencies in the association of PPARG polymorphisms and body weight.

Adult↗