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1.  Sociodemographic distribution of non-communicable disease risk factors in rural Uganda: a cross-sectional study 
Non-communicable diseases (NCDs) are rapidly becoming leading causes of morbidity and mortality in low and middle-income countries, including those in sub-Saharan Africa. By contrast to high-income countries, the sociodemographic distribution, including socioeconomic inequalities, of NCDs and their risk factors is unclear in sub-Saharan Africa, particularly among rural populations.
We undertook a cross-sectional population-based survey of 7809 residents 13 years or older in the General Population Cohort in south-western rural Uganda. Information on behavioural, physiological, and biochemical risk factors was obtained using standardised methods as recommended by the WHO STEPwise Approach to Surveillance. Socioeconomic status (SES) was determined by principal component analysis including household features, ownership, and occupation and education of the head of household.
SES was found to be associated with NCD risk factors in this rural population. Smoking, alcohol consumption (men only), and low HDL-cholesterol were more common among those of lower SES. For example, the prevalence of smoking decreased fourfold from the lowest to highest SES groups, from 22.0% to 5.7% for men and 2.2% to 0.4% for women. By contrast, overweight, raised blood pressure, raised HbA1c (women only), and raised cholesterol were more common among those of higher SES. For example the prevalence of overweight increased fivefold from 2.1% to 10.1% for men and twofold from 12.0% to 23.4% for women from the lowest to highest SES groups. However, neither low physical activity nor fruit, vegetable, or staples consumption was associated with SES. Furthermore, associations between NCD risk factors and SES were modified by age and sex.
Within this rural population NCD risk factors are common and vary both inversely and positively across the socioeconomic status gradient. A better understanding of the determinants of the sociodemographic distribution of NCDs and their risk factors in rural sub-Saharan African populations will help identify populations at most risk of developing NCDs and help plan interventions to reduce their burden.
PMCID: PMC4234905  PMID: 24191304
epidemiology; public health; sub-Saharan Africa; Africa; Uganda; sociodemographic; socioeconomic status; non-communicable diseases; NCDs; chronic diseases; risk factors; epidemiological transition
2.  The general population cohort in rural south-western Uganda: a platform for communicable and non-communicable disease studies 
The General Population Cohort (GPC) was set up in 1989 to examine trends in HIV prevalence and incidence, and their determinants in rural south-western Uganda. Recently, the research questions have included the epidemiology and genetics of communicable and non-communicable diseases (NCDs) to address the limited data on the burden and risk factors for NCDs in sub-Saharan Africa. The cohort comprises all residents (52% aged ≥13years, men and women in equal proportions) within one-half of a rural sub-county, residing in scattered houses, and largely farmers of three major ethnic groups. Data collected through annual surveys include; mapping for spatial analysis and participant location; census for individual socio-demographic and household socioeconomic status assessment; and a medical survey for health, lifestyle and biophysical and blood measurements to ascertain disease outcomes and risk factors for selected participants. This cohort offers a rich platform to investigate the interplay between communicable diseases and NCDs. There is robust infrastructure for data management, sample processing and storage, and diverse expertise in epidemiology, social and basic sciences. For any data access enquiries you may contact the director, MRC/UVRI, Uganda Research Unit on AIDS by email to or the corresponding author.
PMCID: PMC3600628  PMID: 23364209
Data resource profile; general population cohort; communicable and non-communicable diseases; Uganda
3.  Genetic variants influencing circulating lipid levels and risk of coronary artery disease 
Genetic studies might provide new insights into the biological mechanisms underlying lipid metabolism and risk of CAD. We therefore conducted a genome-wide association study to identify novel genetic determinants of LDL-c, HDL-c and triglycerides.
Methods and results
We combined genome-wide association data from eight studies, comprising up to 17,723 participants with information on circulating lipid concentrations. We did independent replication studies in up to 37,774 participants from eight populations and also in a population of Indian Asian descent. We also assessed the association between SNPs at lipid loci and risk of CAD in up to 9,633 cases and 38,684 controls.
We identified four novel genetic loci that showed reproducible associations with lipids (P values 1.6 × 10−8 to 3.1 × 10−10). These include a potentially functional SNP in the SLC39A8 gene for HDL-c, a SNP near the MYLIP/GMPR and PPP1R3B genes for LDL-c and at the AFF1 gene for triglycerides. SNPs showing strong statistical association with one or more lipid traits at the CELSR2, APOB, APOE-C1-C4-C2 cluster, LPL, ZNF259-APOA5-A4-C3-A1 cluster and TRIB1 loci were also associated with CAD risk (P values 1.1 × 10−3 to 1.2 × 10−9).
We have identified four novel loci associated with circulating lipids. We also show that in addition to those that are largely associated with LDL-c, genetic loci mainly associated with circulating triglycerides and HDL-c are also associated with risk of CAD. These findings potentially provide new insights into the biological mechanisms underlying lipid metabolism and CAD risk.
PMCID: PMC3891568  PMID: 20864672
lipids; lipoproteins; genetics; epidemiology
4.  Association of HIV and ART with cardiometabolic traits in sub-Saharan Africa: a systematic review and meta-analysis 
Background Sub-Saharan Africa (SSA) has the highest burden of HIV in the world and a rising prevalence of cardiometabolic disease; however, the interrelationship between HIV, antiretroviral therapy (ART) and cardiometabolic traits is not well described in SSA populations.
Methods We conducted a systematic review and meta-analysis through MEDLINE and EMBASE (up to January 2012), as well as direct author contact. Eligible studies provided summary or individual-level data on one or more of the following traits in HIV+ and HIV-, or ART+ and ART- subgroups in SSA: body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TGs) and fasting blood glucose (FBG) or glycated hemoglobin (HbA1c). Information was synthesized under a random-effects model and the primary outcomes were the standardized mean differences (SMD) of the specified traits between subgroups of participants.
Results Data were obtained from 49 published and 3 unpublished studies which reported on 29 755 individuals. HIV infection was associated with higher TGs [SMD, 0.26; 95% confidence interval (CI), 0.08 to 0.44] and lower HDL (SMD, −0.59; 95% CI, −0.86 to −0.31), BMI (SMD, −0.32; 95% CI, −0.45 to −0.18), SBP (SMD, −0.40; 95% CI, −0.55 to −0.25) and DBP (SMD, −0.34; 95% CI, −0.51 to −0.17). Among HIV+ individuals, ART use was associated with higher LDL (SMD, 0.43; 95% CI, 0.14 to 0.72) and HDL (SMD, 0.39; 95% CI, 0.11 to 0.66), and lower HbA1c (SMD, −0.34; 95% CI, −0.62 to −0.06). Fully adjusted estimates from analyses of individual participant data were consistent with meta-analysis of summary estimates for most traits.
Conclusions Broadly consistent with results from populations of European descent, these results suggest differences in cardiometabolic traits between HIV-infected and uninfected individuals in SSA, which might be modified by ART use. In a region with the highest burden of HIV, it will be important to clarify these findings to reliably assess the need for monitoring and managing cardiometabolic risk in HIV-infected populations in SSA.
PMCID: PMC3887568  PMID: 24415610
HIV; ART; cardiometabolic disease; sub-Saharan Africa
5.  Prospective study of insulin-like growth factor-I, insulin-like growth factor-binding protein 3, genetic variants in the IGF1 and IGFBP3 genes and risk of coronary artery disease 
Although experimental studies have suggested that insulin-like growth factor I (IGF-I) and its binding protein IGFBP-3 might have a role in the aetiology of coronary artery disease (CAD), the relevance of circulating IGFs and their binding proteins in the development of CAD in human populations is unclear. We conducted a nested case-control study, with a mean follow-up of six years, within the EPIC-Norfolk cohort to assess the association between circulating levels of IGF-I and IGFBP-3 and risk of CAD in up to 1,013 cases and 2,055 controls matched for age, sex and study enrolment date. After adjustment for cardiovascular risk factors, we found no association between circulating levels of IGF-I or IGFBP-3 and risk of CAD (odds ratio: 0.98 (95% Cl 0.90-1.06) per 1 SD increase in circulating IGF-I; odds ratio: 1.02 (95% Cl 0.94-1.12) for IGFBP-3). We examined associations between tagging single nucleotide polymorphisms (tSNPs) at the IGF1 and IGFBP3 loci and circulating IGF-I and IGFBP-3 levels in up to 1,133 cases and 2,223 controls and identified three tSNPs (rs1520220, rs3730204, rs2132571) that showed independent association with either circulating IGF-I or IGFBP-3 levels. In an assessment of 31 SNPs spanning the IGF1 or IGFBP3 loci, none were associated with risk of CAD in a meta-analysis that included EPIC-Norfolk and eight additional studies comprising up to 9,319 cases and 19,964 controls. Our results indicate that IGF-I and IGFBP-3 are unlikely to be importantly involved in the aetiology of CAD in human populations.
PMCID: PMC3166154  PMID: 21915365
Epidemiology; Genetics of cardiovascular disease; Risk factors; IGF1; IGFBP3
6.  The V103I polymorphism of the MC4R gene and obesity: population based studies and meta-analysis of 29 563 individuals 
Previous studies have suggested that a variant in the melanocortin-4 receptor (MC4R) gene is important in protecting against common obesity. Larger studies are needed, however, to confirm this relation.
We assessed the association between the V103I polymorphism in the MC4R gene and obesity in three UK population based cohort studies, totalling 8,304 individuals. We also did a meta-analysis of relevant studies, involving 10,975 cases and 18,588 controls, to place our findings in context.
In an analysis of all studies, individuals carrying the isoleucine allele had an 18% (95% CI 4-30%, p=0·015) lower risk of obesity compared with noncarriers. There was no heterogeneity among studies and no apparent publication bias.
This study confirms that the V103I polymorphism protects against human obesity at a population level. As such it provides proof of principle that specific gene variants may, at least in part, explain susceptibility and resistance to common forms of human obesity. A better understanding of the mechanisms underlying this association will help determine whether changes in MC4R activity have therapeutic potential.
PMCID: PMC2683751  PMID: 17356525
7.  Socioeconomic position and risk of short-term weight gain: Prospective study of 14,619 middle-aged men and women 
BMC Public Health  2008;8:112.
The association between socioeconomic position in middle age and risk of subsequent, short-term weight gain is unknown. We therefore assessed this association in a prospective population based cohort study in Norfolk, UK.
We analysed data on 14,619 middle-aged men and women (aged between 40–75 at baseline) with repeated objective measures of weight and height at baseline (1993–1997) and follow up (1998–2000).
During follow up 5,064 people gained more than 2.5 kg. Compared with the highest social class, individuals in the lowest social class had around a 30% greater risk of gaining more than 2.5 kg (OR 1.29; 95% CI 1.11–1.51; p for trend = 0.002). This association remained statistically significant following adjustment for sex, age, baseline BMI, smoking, and follow up time (OR 1.25; CI 1.07–1.46; p for trend <0.001). We also found no material difference between unadjusted models and those including all confounders and potential mediators.
Individuals of low socioeconomic position are at greatest risk of gaining weight during middle age, which is not explained by classical correlates of socioeconomic position and risk factors for obesity.
PMCID: PMC2323377  PMID: 18400100

Results 1-7 (7)