Genotype and phenotype correlations in diabetic patients in Uruguay

ABSTRACT. To differentiate among different types of diabetes is becom-ing an increasingly challenging task. We investigated whether the patient’s genetic profile is useful to identify the particular type of diabetes, to deter-mine the corresponding hyperglycemia pathogenesis and treat accordingly. Three hundred and thirty-eight diabetic patients, diagnosed according to American Diabetes Association criteria, were recruited from 2004 to 2008 in diabetes health reference centers. We analyzed the major gene for type 1 diabetes susceptibility (HLA DQ/DR). In order to improve our understand-ing of the pathogenesis of the resulting hyperglycemia and to implement a more adequate treatment for the patients, we reclassified our sample ac-1353 ©FUNPEC-RP www.funpecrp.com.brGenetics and Molecular Research 8 (4): 1352-1358 (2009) Genotype and phenotype correlations in diabetic patients cording to the presence or absence of the genetic markers. We found that a higher percentage of people than expected have immunological disease, in

On the relevance of the “genetics-based” approach to medicine for sociological perspectives on medical specialization

This paper draws on a study on the development of medical genetics as a medical specialism in the UK and Canada to reflect on how local and national contexts affect specialty formation. The paper begins by supporting earlier findings in the literature that stress, first, technological innovations as driving specialty formation, and, second, the domination of physicians in the division of medical labour. Beyond this, however, the paper explores the specific circumstances under which geneticists set about turning their work into a medical specialism based on a “genetics-based approach” to illness and how “medical genetics” as a specialism was assessed and configured to fit national and regional health service requirements

DNMT3B rs1569686 and rs2424913 gene polymorphisms are associated with positive family history of preterm birth and smoking status

Aim To evaluate the association between spontaneous preterm birth (SPTB) and DNA methyltransferase (DNMT)1, 3A, 3B, and 3L gene polymorphisms, and their contribution to the clinical characteristics of women with SPTB and their newborns. Methods This case-control study, conducted in 2018, enrolled 162 women with SPTB and 162 women with term delivery. DNMT1 rs2228611, DNMT3A rs1550117, DNMT3B rs1569686, DNMT3B rs2424913, and DNMT3L rs2070565 single nucleotide polymorphisms were genotyped using polymerase chain reaction and restriction fragment length polymorphism methods. The clinical characteristics included in the analysis were family history of preterm birth, maternal smoking, maternal age, gestational week at delivery, and fetal birth weight.Results DNMT gene polymorphisms were not significantly associated with SPTB. DNMT3B rs1569686 and rs2424913 minor alleles (T) were significantly more frequent in women with familial PTB than in women with non-familial PTB, increasing the odds for familial PTB 3.30 and 3.54 times under dominant genetic models. They were also significantly more frequent in women with SPTB who smoked before pregnancy, reaching the most significant association under additive genetic models (odds ratio 6.86, 95% confidence interval 2.25-20.86, P < 0.001; odds ratio 3.77, 95% confidence interval 1.36-10.52, P = 0.011, respectively). Conclusions DNMT3B rs1569686 and rs2424913 gene polymorphisms might be associated with positive family history of PTB and smoking status

Genetic services and attitudes in primary care pediatrics

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102660/1/ajmga36339.pd

Trends in Folic Acid Awareness and Behavior in the United States: The Gallup Organization for the March of Dimes Foundation Surveys, 1995–2005

Objective: To summarize changes in folic acid awareness, knowledge, and behavior among women of childbearing age in the United States since the U.S. Public Health Service (USPHS) 1992 folic acid recommendation and later fortification. Methods: Random-digit dialed telephone surveys were conducted of approximately 2000 women (per survey year) aged 18–45 years from 1995–2005 in the United States. Results: The percentage of women reporting having heard or read about folic acid steadily increased from 52% in 1995 to 84% in 2005. Of all women surveyed in 2005, 19% knew folic acid prevented birth defects, an increase from 4% in 1995. The proportion of women who reported learning about folic acid from health care providers increased from 13% in 1995 to 26% in 2005. The proportion of all women who reported taking a vitamin supplement containing folic acid increased slightly from 28% in 1995 to 33% in 2005. Among women who were not pregnant at the time of the survey in 2005, 31% reported taking a vitamin containing folic acid daily compared with 25% in 1995. Conclusions: The percentage of women taking folic acid daily has increased modestly since 1995. Despite this increase, the data show that the majority of women of childbearing age still do not take a vitamin containing folic acid daily. Health care providers and maternal child health professionals must continue to promote preconceptional health among all women of childbearing age, and encourage them to take a vitamin containing folic acid daily

A toolkit for incorporating genetics into mainstream medical services: Learning from service development pilots in England

Background: As advances in genetics are becoming increasingly relevant to mainstream healthcare, a major challenge is to ensure that these are integrated appropriately into mainstream medical services. In 2003, the Department of Health for England announced the availability of start-up funding for ten 'Mainstreaming Genetics' pilot services to develop models to achieve this. Methods: Multiple methods were used to explore the pilots' experiences of incorporating genetics which might inform the development of new services in the future. A workshop with project staff, an email questionnaire, interviews and a thematic analysis of pilot final reports were carried out. Results: Seven themes relating to the integration of genetics into mainstream medical services were identified: planning services to incorporate genetics; the involvement of genetics departments; the establishment of roles incorporating genetic activities; identifying and involving stakeholders; the challenges of working across specialty boundaries; working with multiple healthcare organisations; and the importance of cultural awareness of genetic conditions. Pilots found that the planning phase often included the need to raise awareness of genetic conditions and services and that early consideration of organisational issues such as clinic location was essential. The formal involvement of genetics departments was crucial to success; benefits included provision of clinical and educational support for staff in new roles. Recruitment and retention for new roles outside usual career pathways sometimes proved difficult. Differences in specialties' working practices and working with multiple healthcare organisations also brought challenges such as the 'genetic approach' of working with families, incompatible record systems and different approaches to health professionals' autonomous practice. 'Practice points' have been collated into a Toolkit which includes resources from the pilots, including job descriptions and clinical tools. These can be customised for reuse by other services. Conclusions: Healthcare services need to translate advances in genetics into benefits for patients. Consideration of the issues presented here when incorporating genetics into mainstream medical services will help ensure that new service developments build on the body of experience gained by the pilots, to provide high quality services for patients with or at risk of genetic conditions

Neurogenetics of Dynamic Connectivity Patterns Associated With Obsessive-Compulsive Symptoms in Healthy Children

Obsessive-compulsive symptoms (OCSs) during childhood predispose to obsessive-compulsive disorder and have been associated with changes in brain circuits altered in obsessive-compulsive disorder samples. OCSs may arise from disturbed glutamatergic neurotransmission, impairing cognitive oscillations and promoting overstable functional states. A total of 227 healthy children completed the Obsessive Compulsive Inventory-Child Version and underwent a resting-state functional magnetic resonance imaging examination. Genome-wide data were obtained from 149 of them. We used a graph theory-based approach and characterized associations between OCSs and dynamic functional connectivity (dFC). dFC evaluates fluctuations over time in FC between brain regions, which allows characterizing regions with stable connectivity patterns (attractors). We then compared the spatial similarity between OCS-dFC correlation maps and mappings of genetic expression across brain regions to identify genes potentially associated with connectivity changes. In post hoc analyses, we investigated which specific single nucleotide polymorphisms of these genes moderated the association between OCSs and patterns of dFC. OCSs correlated with decreased attractor properties in the left ventral putamen and increased attractor properties in (pre)motor areas and the left hippocampus. At the specific symptom level, increased attractor properties in the right superior parietal cortex correlated with ordering symptoms. In the hippocampus, we identified two single nucleotide polymorphisms in glutamatergic neurotransmission genes (GRM7, GNAQ) that moderated the association between OCSs and attractor features. We provide evidence that in healthy children, the association between dFC changes and OCSs may be mapped onto brain circuits predicted by prevailing neurobiological models of obsessive-compulsive disorder. Moreover, our findings support the involvement of glutamatergic neurotransmission in such brain network changes

CD4^+ -Central Memory and Effector Memory T Cells in Patients with Asthma

Asthma is associated with chronic airway inflammation, suggesting that its pathogenesis is driven by type 2 helper T (Th2) cells among memory/effector CD4^+ T, cells. CCR4, a chemokine receptor, is considered a preferential marker for Th2 cells. Another chemokine receptor, CCR7, is regarded to be a suitable molecule for T-cell homing to lymph nodes. Recent studies have demonstrated that memory T cells are subdivided into central memory T cells (TCMs) and effector memory T cell (TEMs), designated as CCR7^+ CD62L^+ CD45RA^- and CCR7^- CD62L^- CD45RA^-, respectively. Nevertheless, the properties of TCMs and TEMs in allergic diseases remains unknown. This study focused on the cytokine production and the populations and survival of CD4^+ TCMs and CD4^+ TEMs in patients with asthma (n=3-5), as compared with those in healthy controls (n=4-5). We found that the population of TEMs in asthma was greater than that in healthy control. IL-4-producing cells among both activated TCMs and TEMs and IFN-γ-producing cells among TEMs were more abundant in asthma than in healthy control. Apoptotic cells stained with annexin V and propidium iodide (PI) were more numerous among both TCMs and TEMs in asthma than in healthy control after stimulation with both phorbol myristate acetate and ionomycin. Although CCR4^+ cell populations among TCMs and TEMs were similar in patients with asthma and healthy controls, cytokine-production profiles differed significantly. Namely, CCR4^+ (but not CCR4^-) TCMs and TEMs produced IL-4 and CCR4^+(but not CCR4^-) TCMs produced IFN-γ in both asthma and healthy control. In contrast, both CCR4^+ and CCR4^- TEMs produced IFN-γ. The production levels of IL-4 and IFN-γ by each subpopulation were greater in asthma than in healthy control. Our results suggest that increased CCR4^+-TEMs in peripheral blood accumulate in the lung and to play an important role in the development and maintenance of airway inflammation in asthma. To our knowledge, this is the first study to investigate CCR4^+ TCMs and TEMs in bronchial asthma and healthy controls