Magellan Guewo-Fokeng

Genetic risk of type 2 diabetes in populations of the African continent: A systematic review and meta-analyses

BACKGROUND Type 2 diabetes (T2D) is growing faster in Africa than anywhere else, driven by the dual effects of genetic and environmental factors. We conducted a systematic review and meta-analyses of published studies on genetic markers of T2D in populations within Africa. METHODS Multiple databases were searched for studies of genetic variants associated with T2D in populations living in Africa. Studies reporting on the association of a genetic marker with T2D or indicators of glycaemia were included. Data were extracted on study design and characteristics, genetic determinants, effect estimates of associations with T2D. FINDINGS Overall, 100 polymorphisms in 57 genes have been investigated in relation with T2D in populations within Africa, in 60 studies. Almost all studies used the candidate gene approach, with >88% published during 2006-2014 and 70% (42/60) originating from Tunisia and Egypt. Polymorphisms in ACE, AGRP, eNOS, GSTP1, HSP70-2, MC4R, MTHFR, PHLPP, POL1, TCF7L2, and TNF-α gene were found to be associated with T2D, with overlapping effect on various cardiometabolic traits. The polymorphisms investigated in multiple studies mostly had consistent effects across studies, with only modest or no statistical heterogeneity. Effect sizes were modestly significant [e.g., odd ratio 1.49 (95%CI 1.33-1.66) for TCF7L2 (rs7903146)]. Underpowered genome-wide studies revealed no diabetes risk loci specific to African populations. INTERPRETATION Current evidence on the genetic markers of T2D in African populations mostly originate from North African countries, is overall scanty and largely insufficient to reliably inform the genetic architecture of T2D across Africa.

The Pro12Ala polymorphism in the PPAR-γ2 gene is not associated to obesity and type 2 diabetes mellitus in a Cameroonian population

BackgroundPeroxisome proliferator-activated receptor gamma 2 (PPAR-γ2) is a transcription factor with a key role in adipocyte differentiation, lipid storage and glucose homeostasis. The Ala allele of the common Pro12Ala polymorphism in the isoform PPAR-γ2 is at the center of many controversies because in some populations, it has been observed to be associated with T2DM or obesity but, not in others. The aim of this study was to investigate the association of Pro12Ala polymorphism in the PPAR-γ2 gene with susceptibility to obesity or T2DM in a Cameroonian population.MethodsThis case-control study included 62 obese, 60 T2DM patients and 120 controls (60 non obese and 60 patients without T2DM), all unrelated and of Cameroonian origin. PPAR-γ2 was examined by genotyping for Pro12Ala using the Restriction Fragment Length Polymorphism - Polymerase Chain Reaction (PCR - RFLP).ResultsA portion of the 270 base pair bands of the PPAR-γ2 gene was successfully amplified. The Ala12 variant was totally absent from the study population, all participants being homozygote Pro/Pro.ConclusionPPAR-γ2 Pro12Ala gene polymorphism may not be associated with obesity and T2DM. These results suggest that, PPAR-γ2 is unlikely a major gene for obesity or T2DM in the study population.

Insulin resistance and associated factors among HIV-infected patients in sub-Saharan Africa: a cross sectional study from Cameroon

Introduction: little is known on the magnitude and correlates of insulin resistance in HIV-infected people in Africa. We determined the prevalence of insulin resistance and investigated associated factors in HIV-infected adult Cameroonians. Methods: we conducted a cross-sectional studyat the Yaounde Central Hospital, Cameroon; during which we enrolled HIV-infected people aged 30 to 74 years with no previous history of cardiovascular disease. The homeostatic model assessment of insulin resistance (HOMA-IR) index served to assess insulin sensitivity with insulin resistance defined by values of 2.1 or higher. Results: we included 452 patients (20% men). Their mean age was 44.4 ± 9.8 years and 88.5% of them were on antiretroviral therapy (93.3% on first line regimen including Zidovudine, lamivudine and Efavirenz/Nevirapine). Of all participants, 28.5% were overweight, 19.5% had obesity and 2.0% had diabetes. The prevalence of insulin resistance was 47.3% without any difference between patients on ART and those ART-naive (48.5% vs. 38.5%; p = 0.480). Obesity was the only factor independently associated with insulin resistance (adjusted odds ratio: 2.28; 95% confidence interval: 1.10-4.72). Conclusion: insulin resistance is present in nearly half of HIV-infected patients in Cameroon despite a low prevalence rate of diabetes, and is associated with obesity.

Genetic polymorphisms of organic cation transporters 1 (OCT1) and responses to metformin therapy in individuals with type 2 diabetes mellitus: a systematic review protocol

BackgroundMetformin is one of the most commonly used drugs for type 2 diabetes mellitus (T2DM). Despite its efficacy and safety, metformin is frequently associated with highly variable glycemic responses, which is hypothesized to be the result of genetic variations in its transport by organic cation transporters (OCTs). This systematic review aims to highlight and summarize the overall effects of OCT1 polymorphisms on therapeutic responses to metformin and to evaluate their potential role in terms of interethnic differences with metformin responses.Methods/designWe will systematically review observational studies reporting on the genetic association between OCT1 polymorphisms and metformin responses in T2DM patients. A comprehensive search strategy formulated with the help of a librarian will be used to search MEDLINE via PubMed, Embase, and CINAHL for relevant studies published between January 1990 and July 2017. Two review authors will independently screen titles and abstracts in duplicate, extract data, and assess the risk of bias with discrepancies resolved by discussion or arbitration of a third review author. Mined data will be grouped according to OCT1 polymorphisms, and their effects on therapeutic responses to metformin will be narratively synthesized. If sufficient numbers of homogeneous studies are scored, meta-analyses will be performed to obtain pooled effect estimates. Funnel plots analysis and Egger’s test will be used to assess publication bias. This study will be reported according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines.DiscussionThis review will summarize the genetic effects of OCT1 polymorphisms associated with variabilities in glycemic responses to metformin. The findings of this study could help to develop genetic tests that could predict a person’s response to metformin treatment and create personalized drugs with greater efficacy and safety.Systematic review registrationRegistration number: PROSPERO, CRD42017079978

Investigation of the association between the TCF7L2 rs7903146 (C/T) gene polymorphism and obesity in a Cameroonian population: a pilot study

ObjectiveThis study aimed at investigating the association between the rs7903146 (C/T) polymorphism of the TCF7L2 gene with obesity in a Cameroonian population.MethodThis was a case-control pilot study including 61 obese and 61 non-obese Cameroonian adults. Anthropometric indices of obesity, blood pressure, fasting blood glucose, and blood lipids were measured. The rs7903146 (C/T) polymorphism of the TCF7L2 gene was genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and genotypes were correlated with clinical and biological parameters.ResultsThe T allele was predominant in the study population with a frequency of 93%. No statistically significant difference was however observed between the genotypic (p = 0.50) and allelic frequencies (p = 0.58) of obese and non-obese subjects. Comparison of clinical and biochemical parameters of C allele carriers (CX = CC + CT) with those of TT genotype showed that there was no significant difference between the lipid profile of these two groups.ConclusionThe rs7903146 (C/T) polymorphism of the TCF7L2 gene might not be associated with obesity in the Cameroonian population.

Relationship between estimated cardiovascular disease risk and insulin resistance in a black African population living with HIV: a cross-sectional study from Cameroon

Objectives Cardiovascular disease (CVD) and metabolic diseases are growing concerns among patients with HIV infection as a consequence of the improving survival of this population. We aimed to assess the relationship between CVD risk and insulin resistance in a group of black African individuals with HIV infection. Methods This cross-sectional study involved patients with HIV infection aged 30–74 years and followed up at the Yaoundé Central Hospital, Cameroon. Absolute CVD risk was calculated using the Framingham and the DAD CVD risk equations while the HOMA-IR index was used to assess insulin resistance (index ≥2.1). Results A total of 452 patients (361 women; 80%) were screened. The mean age was 44.4 years and most of the respondents were on antiretroviral therapy (88.5%). The median 5-year cardiovascular risk was 0.7% (25th−75th percentiles: 0.2–2.0) and 0.6% (0.3–1.3) according to the Framingham and DAD equations respectively. Of all participants, 47.3% were insulin resistant. The Framingham equation derived absolute CVD risk was significantly associated with insulin resistance; while no linear association was found using the DAD equation. Conclusion The relationship between cardiovascular risk and insulin resistance in black African patients with HIV infection seems to depend on the cardiovascular risk equation used.