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

Genotype patterns at CLU, CR1, PICALM and APOE, cognition and Mediterranean diet: the PREDIMED-NAVARRA trial

The traditional Mediterranean diet (MedDiet) has shown beneficial effects on cognitive decline. Nevertheless, diet–gene interactions have been poorly evaluated. We aimed to investigate diet–gene interaction in the PREDIMED-NAVARRA randomized trial. A total of 522 participants (67 ± 6 years at baseline) enrolled in the PREDIMED-NAVARRA trial were randomly allocated to one of three diets: two MedDiets (supplemented with either extra-virgin olive oil or nuts) or a low-fat diet. They were evaluated with the Mini-Mental State Examination (MMSE) and the Clock Drawing Test (CDT) after 6.5 years of intervention. Subjects were genotyped for CR1-rs3818361, CLU-rs11136000, PICALM-rs3851179 and Apolipoprotein E (ApoE) genes. We studied MedDiet–gene interactions for cognition and assessed the effect of the MedDiet on cognition across different genetic profiles. A significant interaction (p = 0.041) between CLU-rs11136000 and the MedDiet intervention on the MMSE was found with a beneficial effect of MedDiet among carriers of the T minor allele (B = 0.97, 95 % CI 0.45–1.49). Similar effect was observed for CR1-rs3818361, but no significant interaction was observed (p = 0.335). For PICALM-rs3851179, the MedDiet intervention showed a beneficial effect in both genotype groups. No apparent interaction was found for the CDT between intervention and gene variants. Similarly, participants randomly allocated to MedDiet groups, with favorable profiles of CR1, CLU and PICALM genes, significantly improved CDT scores compared to controls with the same genetic profile. Cognitive performance was better for non-ApoE4 and for ApoE4 carriers of MedDiet groups compared to controls, but for CDT performance, we only found statistical significant differences for non-ApoE4 carriers. A MedDiet intervention modulates the effect of genetic factors on cognition. The effect of MedDiet might be greater for subjects with a more favorable genetic profile

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

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

Food consumption, nutrient intake, and dietary patterns in Ghanaian migrants in Europe and their compatriots in Ghana.

Background: West African immigrants in Europe are disproportionally affected by metabolic conditions compared to European host populations. Nutrition transition through urbanisation and migration may contribute to this observations, but remains to be characterised. Objective: We aimed to describe the dietary behaviour and its socio-demographic factors among Ghanaian migrants in Europe and their compatriots living different Ghanaian settings. Methods: The multi-centre, cross-sectional RODAM (Research on Obesity and Diabetes among African Migrants) study was conducted among Ghanaian adults in rural and urban Ghana, and Europe. Dietary patterns were identified by principal component analysis. Results: Contributions of macronutrient to the daily energy intake was different across the three study sites. Three dietary patterns were identified. Adherence to the 'mixed' pattern was associated with female sex, higher education, and European residency. The 'rice, pasta, meat, and fish' pattern was associated with male sex, younger age, higher education, and urban Ghanaian environment. Adherence to the 'roots, tubers, and plantain' pattern was mainly related to rural Ghanaian residency. Conclusion: We observed differences in food preferences across study sites: in rural Ghana, diet concentrated on starchy foods; in urban Ghana, nutrition was dominated by animal-based products; and in Europe, diet appeared to be highly diverse

Peripheral insulin resistance rather than beta cell dysfunction accounts for geographical differences in impaired fasting blood glucose among sub-Saharan African individuals: findings from the RODAM study.

AIMS/HYPOTHESIS: The aim of this study was to assess the extent to which insulin resistance and beta cell dysfunction account for differences in impaired fasting blood glucose (IFBG) levels in sub-Saharan African individuals living in different locations in Europe and Africa. We also aimed to identify determinants associated with insulin resistance and beta cell dysfunction among this population. METHODS: Data from the cross-sectional multicentre Research on Obesity and Diabetes among African Migrants (RODAM) study were analysed. Participants included Ghanaian individuals without diabetes, aged 18-96 years old, who were residing in Amsterdam (n = 1337), Berlin (n = 502), London (n = 961), urban Ghana (n = 1309) and rural Ghana (n = 970). Glucose and insulin were measured in fasting venous blood samples. Anthropometrics were assessed during a physical examination. Questionnaires were used to assess demographics, physical activity, smoking status, alcohol consumption and energy intake. Insulin resistance and beta cell function were determined using homeostatic modelling (HOMA-IR and HOMA-B, respectively). Logistic regression analysis was used to study the contribution of HOMA-IR and inverse HOMA-B (beta cell dysfunction) to geographical differences in IFBG (fasting glucose 5.6-6.9 mmol/l). Multivariate linear regression analysis was used to identify determinants associated with HOMA-IR and inverse HOMA-B. RESULTS: IFBG was more common in individuals residing in urban Ghana (OR 1.41 [95% CI 1.08, 1.84]), Amsterdam (OR 3.44 [95% CI 2.69, 4.39]) and London (OR 1.58 [95% CI 1.20 2.08), but similar in individuals living in Berlin (OR 1.00 [95% CI 0.70, 1.45]), compared with those in rural Ghana (reference population). The attributable risk of IFBG per 1 SD increase in HOMA-IR was 69.3% and in inverse HOMA-B was 11.1%. After adjustment for HOMA-IR, the odds for IFBG reduced to 0.96 (95% CI 0.72, 1.27), 2.52 (95%CI 1.94, 3.26) and 1.02 (95% CI 0.78, 1.38) for individuals in Urban Ghana, Amsterdam and London compared with rural Ghana, respectively. In contrast, adjustment for inverse HOMA-B had very minor impact on the ORs of IFBG. In multivariate analyses, BMI (β = 0.17 [95% CI 0.11, 0.24]) and waist circumference (β = 0.29 [95%CI 0.22, 0.36]) were most strongly associated with higher HOMA-IR, whereas inverse HOMA-B was most strongly associated with age (β = 0.20 [95% CI 0.16, 0.23]) and excess alcohol consumption (β = 0.25 [95% CI 0.07, 0.43]). CONCLUSIONS/INTERPRETATION: Our findings suggest that insulin resistance, rather than beta cell dysfunction, is more important in accounting for the geographical differences in IFBG among sub-Saharan African individuals. We also show that BMI and waist circumference are important factors in insulin resistance in this population

Food variety, dietary diversity, and type 2 diabetes in a multi-center cross-sectional study among Ghanaian migrants in Europe and their compatriots in Ghana: the RODAM study.

PURPOSE: The importance of dietary diversification for type 2 diabetes (T2D) risk remains controversial. We investigated associations of between- and within-food group variety with T2D, and the role of dietary diversification for the relationships between previously identified dietary patterns (DPs) and T2D among Ghanaian adults. METHODS: In the multi-center cross-sectional Research on Obesity and Diabetes among African Migrants (RODAM) Study (n = 3810; Ghanaian residence, 56%; mean age, 46.2 years; women, 63%), we constructed the Food Variety Score (FVS; 0-20 points), the Dietary Diversity Score (DDS; 0-7 points), and the Diet Quality Index-International (DQI-I) variety component (0-20 points). The associations of these scores, of a "rice, pasta, meat and fish" DP, of a "mixed" DP, and of a "roots, tubers and plantain" DP with T2D were calculated by logistic regression. RESULTS: The FVS was inversely associated with T2D, adjusted for socio-demographic, lifestyle, and anthropometric factors [odds ratio (OR) for T2D per 1 standard deviation (SD) increase: 0.81; 95% confidence interval (CI) 0.71-0.93]. The DDS and the DQI-I variety component were not associated with T2D. There was no association of the "mixed" DP and the "roots, tubers and plantain" DP with T2D. Yet, the "rice, pasta, meat and fish" DP is inversely associated with T2D (OR for T2D per 1 SD increase: 0.82; 95% CI 0.71-0.95); this effect was slightly attenuated by the FVS. CONCLUSIONS: In this Ghanaian population, between-food group variety may exert beneficial effects on glucose metabolism and partially explains the inverse association of the "rice, pasta, meat and fish" DP with T2D

An epigenome-wide association study in whole blood of measures of adiposity among Ghanaians: the RODAM study.

BACKGROUND: Epigenome-wide association studies (EWAS) have identified DNA methylation loci involved in adiposity. However, EWAS on adiposity in sub-Saharan Africans are lacking despite the high burden of adiposity among African populations. We undertook an EWAS for anthropometric indices of adiposity among Ghanaians aiming to identify DNA methylation loci that are significantly associated. METHODS: The Illumina 450k DNA methylation array was used to profile DNA methylation in whole blood samples of 547 Ghanaians from the Research on Obesity and Diabetes among African Migrants (RODAM) study. Differentially methylated positions (DMPs) and differentially methylation regions (DMRs) were identified for BMI and obesity (BMI ≥ 30 kg/m2), as well as for waist circumference (WC) and abdominal obesity (WC ≥ 102 cm in men, ≥88 cm in women). All analyses were adjusted for age, sex, blood cell distribution estimates, technical covariates, recruitment site and population stratification. We also did a replication study of previously reported EWAS loci for anthropometric indices in other populations. RESULTS: We identified 18 DMPs for BMI and 23 for WC. For obesity and abdominal obesity, we identified three and one DMP, respectively. Fourteen DMPs overlapped between BMI and WC. DMP cg00574958 annotated to gene CPT1A was the only DMP associated with all outcomes analysed, attributing to 6.1 and 5.6% of variance in obesity and abdominal obesity, respectively. DMP cg07839457 (NLRC5) and cg20399616 (BCAT1) were significantly associated with BMI, obesity and with WC and had not been reported by previous EWAS on adiposity. CONCLUSIONS: This first EWAS for adiposity in Africans identified three epigenome-wide significant loci (CPT1A, NLRC5 and BCAT1) for both general adiposity and abdominal adiposity. The findings are a first step in understanding the role of DNA methylation in adiposity among sub-Saharan Africans. Studies on other sub-Saharan African populations as well as translational studies are needed to determine the role of these DNA methylation variants in the high burden of adiposity among sub-Saharan Africans

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 40-70years in the multi-centre RODAM study among Ghanaians residing in Ghana and Europe using the Framingham laboratory and non-laboratory and Pooled Cohort Equations (PCE) algorithms. Participants were classified as low, moderate or high risk, corresponding to 20% 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