Steady-state expression of self-regulated genes

Motivation: Regulatory gene networks contain generic modules such as feedback loops that are essential for the regulation of many biological functions. The study of the stochastic mechanisms of gene regulation is instrumental for the understanding of how cells maintain their expression at levels commensurate with their biological role, as well as to engineer gene expression switches of appropriate behavior. The lack of precise knowledge on the steady-state distribution of gene expression requires the use of Gillespie algorithms and Monte-Carlo approximations. Methodology: In this study, we provide new exact formulas and efficient numerical algorithms for computing/modeling the steady-state of a class of self-regulated genes, and we use it to model/compute the stochastic expression of a gene of interest in an engineered network introduced in mammalian cells. The behavior of the genetic network is then analyzed experimentally in living cells. Results: Stochastic models often reveal counter-intuitive experimental behaviors, and we find that this genetic architecture displays a unimodal behavior in mammalian cells, which was unexpected given its known bimodal response in unicellular organisms. We provide a molecular rationale for this behavior, and we implement it in the mathematical picture to explain the experimental results obtained from this network. Contact: [email protected], [email protected] Supplementary information: Supplementary data are available at Bioinformatics onlin

Lifestyle factors modify obesity risk linked to PPARG2 and FTO variants in an elderly population: a cross-sectional analysis in the SUN Project.

Genetic factors may interact with lifestyle factors to modify obesity risk. FTO and PPARG2 are relevant obesogenes. Our aim was to explore the effect of Pro12Ala (rs1801282) of PPARG2 and rs9939609 of FTO on obesity risk and to examine their interaction with lifestyle factors in an elderly population. Subjects (n = 978; aged 69 ± 6) were recruited from the SUN (Seguimiento Universidad de Navarra) Project. DNA was obtained from saliva, and lifestyle and dietary data were collected by validated self-reported questionnaires. Genotyping was assessed by RT-PCR plus allele discrimination. Subjects carrying the Ala allele of PPARG2 gene had a significantly increased obesity risk compared to non-carrier (Pro12Pro) subjects (OR, 1.66; 95 % CI, 1.01-2.74; p = 0.045). Greater obesity risk was also found in inactive or high carbohydrate intake subjects with the Ala12 allele of PPARG2 gene. Interestingly, subjects carrying the Ala allele of the PPARG2 gene and with a high CHO (>246 g/day) intake had an increased obesity risk compared to Pro12Pro subjects (OR, 2.67; 95 % CI, 1.3-5.46; p = 0.007; p for [CHO × PPARG2] interaction = 0.046). Moreover, in subjects with a high CHO intake, the co-presence of the Ala allele of PPARG2 gene and one minor A allele (rs9939609) of FTO gene did increase obesity risk (OR, 3.26; 95 % CI, 1.19-8.89; p = 0.021) when compared to non-carrier (Pro12Pro/TT) subjects. In conclusion, it appears that lifestyle factors may act as effect modifiers for obesity risk linked to Ala12 allele of the PPARG2 gene and the minor A allele of FTO gene in an elderly population

Physical activity and sex modulate obesity risk linked to 3111T/C gene variant of the CLOCK gene in an elderly population: the SUN Project

Genetic factors may interact with physical activity levels to modify obesity risk. Our aim was to explore the effect of rs1801260 SNP (3111T/C) of CLOCK gene, on obesity risk and to examine their interaction with lifestyle factors in an elderly population of the SUN Project. Subjects (n=903, aged 69±6) were recruited from the SUN (“Seguimiento Universidad de Navarra”) Project. DNA was obtained from saliva and lifestyle and dietary data were collected by validated self-reported questionnaires. Genotyping was assessed by RT-PCR plus allele discrimination. A significant interaction between the 3111T/C SNP of CLOCK gene and sex for overweight/obesity risk was observed (p for interaction [Sex*CLOCK] interaction <0.001). Our results showed that women carrying the C allele of CLOCK gene had a decreased overweight/obesity risk compared to non carrier -TT- subjects (OR 0.61, 95% CI: 0.36-1.04, p=0.069). Moreover, the protective effect of the 3111T/C gene variant may be enhanced in those women with a high physical activity practice. We found that women practicing more than 16.8 METs- h/week had a significantly lower overweight/obesity risk (OR 0.36, 95%CI: 0.17-0.79, p=0.011). A significant interaction between the 3111T/C gene variant and physical activity for overweight/obesity risk was observed in women (p for [PA x CLOCK] interaction=0.015). In conclusion, it appears that physical activity levels may act as an effect modifier for overweight/obesity risk linked to the 3111T/C SNP (rs1801260) of the CLOCK gene in an elderly population of the SUN Project

Differences in alcohol consumption and drinking patterns in Ghanaians in Europe and Africa: The RODAM Study

BACKGROUND: Little is known about alcohol consumption among Africans living in rural and urban Africa compared to African migrants in Europe. We compared the patterns of alcohol consumption in a group of Ghanaians living in different locations in Ghana and in Europe and examined the factors associated with drinking alcohol. METHODS: Data were from a cross-sectional study (RODAM) of Ghanaians aged 25-70 years living in rural and urban Ghana and in Amsterdam, Berlin and London. Information on how often participants consumed at least one standard alcoholic drink in the preceding 12 months, the type of alcoholic beverage and the average serving size was obtained using a food propensity questionnaire. The associations between drinking alcohol and socio-demographic variables, and frequency of attending religious services were investigated using logistic regression models stratified by site and sex. For Ghanaians living in Europe, the number of years since migration and acculturation were also included in the model as covariates. RESULTS: 4280 participants (62.2% women) were included in the analyses. In both men and women, the prevalence of drinking and amount of alcohol consumed per day was highest in Berlin (prevalence of drinking 71.0% and 61.7%) and lowest in urban Ghana (41.4% and 26.8%). After adjustment for age and education in both men and women in Europe, those attending religious services less frequently reported higher levels of drinking alcohol than non-attendants (never attend/no religion compared to attending service at least once a week men OR 4.60 95% CI 2.85, 7.44; women OR 1.80 95% CI 1.12, 2.90) p-trend with frequency <0.001 in men; 0.002 in women); this association was seen also in men in rural Ghana (p-trend = 0.001) and women in urban Ghana (p-trend = 0.02). The prevalence of drinking was positively associated with years since migration in both men and women in Europe ((OR per years increase in time lived in Europe 1.25 (95% CI 1.02,1.53) test for trend p = 0.03 in women; OR 1.29 (95% CI 1.03, 1.62 p = 0.03 in men) but no association was found with self-reported measures of acculturation (ethnic identity, cultural orientation or social networks). CONCLUSION: There are marked differences in alcohol consumption between Ghanaians living in Europe and in Ghana suggesting migration has an important influence of drinking patterns and also suggesting the possibility of requiring different strategies in alcohol reduction campaigns among Ghanaians in different locations

Association between socioeconomic position and the prevalence of type 2 diabetes in Ghanaians in different geographic locations: the RODAM study

BACKGROUND: The prevalence of diabetes has been shown to be socially patterned but the direction of the association in low-income countries and among migrant populations in Europe has varied in the literature. This study examined the association between socioeconomic position (SEP) and diabetes in Ghanaians in Europe and in Ghana. METHODS: Data were derived from the multicentre Research on Obesity and Diabetes among African Migrants (RODAM) study of Ghanaian adults aged 25-70 years residing in Europe (Amsterdam, Berlin and London) and in urban and rural Ghana. Educational attainment (elementary, secondary or higher) and occupational class (low or high) were used as indicators of SEP. Age-standardised prevalence of diabetes and prevalence ratios were evaluated separately for men and women of different SEP in Ghana and Europe. RESULTS: A total of 5290 participants were included in the analyses. The prevalence of diabetes decreased with increasing level of education in Ghanaian men and women in Europe and in men in urban Ghana, whereas diabetes prevalence increased with increasing level of education in men and women in rural Ghana. The association between occupational class and the prevalence of diabetes followed a less consistent pattern in men and women in the different locations. CONCLUSIONS: The association of diabetes and SEP differed in rural Ghana compared with urban settings in Ghana and Europe and comparing men and women, highlighting the complex interaction of SEP and the development of diabetes. These findings have important implications for diabetes prevention strategies in Ghanaians in different locations

Smoking prevalence differs by location of residence among Ghanaians in Africa and Europe: The RODAM study

BACKGROUND: Although the prevalence of smoking is low in Ghana, little is known about the effect of migration on smoking. Comparing Ghanaians living in their country of origin to those living in Europe offers an opportunity to investigate smoking by location of residence and the associations between smoking behaviours and migration-related factors. METHODS: Data on a relatively homogenous group of Ghanaians living in London (n = 949), Amsterdam (n = 1400), Berlin (n = 543), rural Ghana (n = 973) and urban Ghana (n = 1400) from the cross-sectional RODAM (Research on Obesity & Diabetes in African Migrants) study were used. Age-standardized prevalence rates of smoking by location of residence and factors associated with smoking among Ghanaian men were estimated using prevalence ratios (PR: 95% CIs). RESULTS: Current smoking was non-existent among women in rural and urban Ghana and London but was 3.2% and 3.3% in women in Amsterdam and Berlin, respectively. Smoking prevalence was higher in men in Europe (7.8%) than in both rural and urban Ghana (4.8%): PR 1.91: 95% CI 1.27, 2.88, adjusted for age, marital status, education and employment. Factors associated with a higher prevalence of smoking among Ghanaian men included European residence, being divorced or widowed, living alone, Islam religion, infrequent attendance at religious services, assimilation (cultural orientation), and low education. CONCLUSION: Ghanaians living in Europe are more likely to smoke than their counterparts in Ghana, suggesting convergence to European populations, although prevalence rates are still far below those in the host populations

Dietary patterns and type 2 diabetes among Ghanaian migrants in Europe and their compatriots in Ghana: the RODAM study

BACKGROUND/OBJECTIVES: We aimed to study the associations of dietary patterns (DPs) with type 2 diabetes (T2D) among Ghanaian adults. SUBJECTS/METHODS: In the multi-centre, cross-sectional RODAM (Research on Obesity and Diabetes among African Migrants) study (n = 4543), three overall DPs ("mixed", "rice, pasta, meat and fish," and "roots, tubers and plantain") and two site-specific DPs per study site (rural Ghana, urban Ghana and Europe) were identified by principal component analysis. The DPs-T2D associations were calculated by logistic regression models. RESULTS: Higher adherence to the "rice, pasta, meat and fish" DP (characterized by legumes, rice/pasta, meat, fish, cakes/sweets, condiments) was associated with decreased odds of T2D, adjusted for socio-demographic factors, total energy intake and adiposity measures (odds ratio (OR)per 1 SD = 0.80; 95% confidence interval (CI) = 0.70-0.92). Similar DPs and T2D associations were discernible in urban Ghana and Europe. In the total study population, neither the "mixed" DP (whole grain cereals, sweet spreads, dairy products, potatoes, vegetables, poultry, coffee/tea, sodas/juices, olive oil) nor the "roots, tubers and plantain" DP (refined cereals, fruits, nuts/seeds, roots/tubers/plantain, fermented maize products, legumes, palm oil, condiments) was associated with T2D. Yet, after the exclusion of individuals with self-reported T2D, the "roots, tubers and plantain" DP was inversely associated with T2D (ORper 1 SD = 0.88; 95% CI = 0.69-1.12). CONCLUSION: In this Ghanaian population, DPs characterized by the intake of legumes, fish, meat and confectionery were inversely associated with T2D. The effect of a traditional-oriented diet (typical staples, vegetables and legumes) remains unclear

Type 2 diabetes mellitus management among Ghanaian migrants resident in three European countries and their compatriots in rural and urban Ghana - The RODAM study

AIMS: To compare Type 2 Diabetes Mellitus (T2DM) awareness, treatment and control between Ghanaians resident in Ghana and Europe. // METHODS: Comparisons were made for the 530 participants of the Research on Obesity and Diabetes among African Migrants (RODAM) study with T2DM (25-70 years) living in Amsterdam, Berlin, London, urban Ghana and rural Ghana. We used logistic regression to assess disparities with adjustment for age, sex and education. // RESULTS: T2DM awareness was 51% in rural Ghana. This was lower than levels in Europe ranging from 73% in London (age-sex adjusted odds ratio (OR) = 2.7; 95%CI = 1.2-6.0) to 79% in Amsterdam (OR = 4.7; 95%CI = 2.3-9.6). T2DM treatment was also lower in rural Ghana (37%) than in urban Ghana (56%; OR = 2.6; 95%CI = 1.3-5.3) and European sites ranging from 67% in London (OR = 3.4; 95%CI = 1.5-7.5) to 73% in Berlin (OR = 6.9; 95%CI = 2.9-16.4). In contrast, T2DM control in rural Ghana (63%) was comparable to Amsterdam and Berlin, but higher than in London (40%; OR = 0.4; 95%CI = 0.2-0.9) and urban Ghana (28%; OR = 0.3; 95%CI = 0.1-0.6). // CONCLUSIONS: Our findings suggest that improved detection and treatment of T2DM in rural Ghana, and improved control for people with diagnosed T2DM in London and urban Ghana warrant prioritization. Further work is needed to understand the factors driving the differences

Cardiovascular disease risk prediction in sub-Saharan African populations - Comparative analysis of risk algorithms in the RODAM study

Background: Validated absolute risk equations are currently recommended as the basis of cardiovascular disease (CVD) risk stratification in prevention and control strategies. However, there is no consensus on appropriate equations for sub-Saharan African populations. We assessed agreement between different cardiovascular risk equations among Ghanaian migrant and home populations with no overt CVD. Methods: The 10-year CVD risks were calculated for 3586 participants aged 40–70 years in the multi-centre RODAM study among Ghanaians residing in Ghana and Europe using the Framingham laboratory and nonlaboratory and Pooled Cohort Equations (PCE) algorithms. Participants were classified as low, moderate or high risk, corresponding to b10%, 10–20% and N20% respectively. Agreement between the risk algorithms was assessed using kappa and correlation coefficients. Results: 19.4%, 12.3% and 5.8% were ranked as high 10-year CVD risk by Framingham non-laboratory, Framingham laboratory and PCE, respectively. The median (25th–75th percentiles) estimated 10-year CVD risk was 9.5% (5.4–15.7), 7.3% (3.9–13.2) and 5.0% (2.3–9.7) for Framingham non-laboratory, Framingham laboratory and PCE, respectively. The concordance between PCE and Framingham non-laboratory was better in the home Ghanaian population (kappa = 0.42, r = 0.738) than the migrant population (kappa = 0.24, r = 0.732) whereas concordance between PCE and Framingham laboratory was better in migrant Ghanaians (kappa = 0.54, r = 0.769) than the home population (kappa = 0.51, r = 0.758). Conclusion: CVD prediction with the same algorithm differs for the migrant and home populations and the interchangeability of Framingham laboratory and non-laboratory algorithms is limited. Validation against CVD outcomes is needed to inform appropriate selection of risk algorithms for use in African ancestry populations