Cally Roper and colleagues analyze the distribution of sulfadoxine resistance mutations and flanking microsatellite loci to trace the emergence and dispersal of drug-resistant Plasmodium falciparum malaria in Africa.

Background To study the relationship between the rs12255372 (G/T) polymorphism of the transcription factor 7-like 2 ( TCF7L2 ) and type 2 diabetes mellitus (T2DM) in a Cameroonian population. Methods This case–control study included 60 T2DM patients and 60 healthy normoglycemic controls, all unrelated and of Cameroonian origin, aged above 40 years (range 40–87). The Restriction Fragment Length Polymorphism - Polymerase Chain Reaction (RFLP-PCR) was used for genotyping. Results The T allele frequency was significantly higher in the diabetic group (0.44) than in the control group (0.17). This allele was significantly associated to a greater risk of developing T2DM as compared to the G allele (OR = 3.92, 95% CI 2.04 – 7.67, p < 0.0001). The codominant (additive) model explained best the risk of developing the disease, as the TT genotype was significantly associated to T2DM when compared to the GG genotype (OR = 4.45, 95% CI 1.64 – 12.83, p = 0.0014). By logistic regression adjusted for age, this OR was 4.33 (95% CI: 1.57 – 11.92, p = 0.005). Conclusion Our findings suggest that the rs12255372 (G/T) polymorphism of the TCF7L2 gene is an important risk factor for T2DM in the Cameroonian population.

BackgroundData on the genetic variants for type 2 diabetes mellitus (T2DM) in sub-Saharan African populations are very scarce. This study aimed to investigate the association of transcription factor 7-like (TCF7L2) with T2DM in a Cameroonian population and explore possible genotype-phenotype correlation.MethodsThis is a case–control study involving 37 T2DM patients and 37 non-diabetic volunteers of Cameroonian ethnicity aged 40 years old and above. We collected clinical and biological data to determine phenotypic traits. TCF7L2 was analyzed by genotyping for rs7903146 (C/T) using PCR-RFLP. Biochemical analyses were performed using a spectrophotometer with Chronolab kits. Statistical analyses were carried out using IBM SPSS, PS and Quanto.ResultsTCF7L2 was associated with T2DM in this Cameroonian population (p = 0.013 for alleles, and p = 0.013 for genotypes). The risk allele was C (9.5% patients vs. 0% healthy controls, OR = 16.56) and the protective allele was T (90.5% patients vs. 100.0% healthy controls, OR = 0.06). The risk genotype was C/T (18.9% patients vs. 0% healthy controls, OR = 18.44), while the protective genotype was T/T (81.1% patients vs. 100.0% healthy controls, OR = 0.054). The statistical power was 99.99%. TCF7L2 was not preferentially associated with a specific disease phenotype.ConclusionTCF7L2 is associated with T2DM in this Cameroonian population. The association is not dependent on a specific T2DM phenotype. Clinical genetic testing for TCF7L2 can help to predict the occurrence of T2DM in Cameroon.

Background Malaria remains highly endemic in Cameroon. The rapid emergence and spread of drug resistance was responsible for the change from monotherapies to artemisinin-based combinations. This systematic review and meta-analysis aimed to determine the prevalence and distribution of Plasmodium falciparum drug resistance markers within an evolving efficacy of anti-malarial drugs in Cameroon from January 1998 to August 2020. Methods The PRISMA-P and PRISMA statements were adopted in the inclusion of studies on single nucleotide polymorphisms (SNPs) of P. falciparum anti-malarial drug resistance genes (Pfcrt, Pfmdr1, Pfdhfr, Pfdhps, Pfatp6, Pfcytb and Pfk13). The heterogeneity of the included studies was evaluated using the Cochran’s Q and I2 statistics. The random effects model was used as standard in the determination of heterogeneity between studies. Results Out of the 902 records screened, 48 studies were included in this aggregated meta-analysis of molecular data. A total of 18,706 SNPs of the anti-malarial drug resistance genes were genotyped from 47,382 samples which yielded a pooled prevalence of 35.4% (95% CI 29.1–42.3%). Between 1998 and 2020, there was significant decline (P < 0.0001 for all) in key mutants including Pfcrt 76 T (79.9%-43.0%), Pfmdr1 86Y (82.7%-30.5%), Pfdhfr 51I (72.2%-66.9%), Pfdhfr 59R (76.5%-67.8%), Pfdhfr 108 N (80.8%-67.6%). The only exception was Pfdhps 437G which increased over time (30.4%-46.9%, P < 0.0001) and Pfdhps 540E that remained largely unchanged (0.0%-0.4%, P = 0.201). Exploring mutant haplotypes, the study observed a significant increase in the prevalence of Pfcrt CVIET mixed quintuple haplotype from 57.1% in 1998 to 57.9% in 2020 (P < 0.0001). In addition, within the same study period, there was no significant change in the triple Pfdhfr IRN mutant haplotype (66.2% to 67.3%, P = 0.427). The Pfk13 amino acid polymorphisms associated with artemisinin resistance were not detected. Conclusions This review reported an overall decline in the prevalence of P. falciparum gene mutations conferring resistance to 4-aminoquinolines and amino alcohols for a period over two decades. Resistance to artemisinins measured by the presence of SNPs in the Pfk13 gene does not seem to be a problem in Cameroon. Systematic review registration PROSPERO CRD42020162620

Background: In this post-hoc analysis, we determined the influence of single nucleotide polymorphisms in host candidate immune genes on the outcome of drug resistant malaria in Cameroon. Methods: Human DNA from 760 patients from a previous clinical trial was subjected to mass spectrometrybased single nucleotide polymorphism (SNP) genotyping. Allele frequencies of candidate immune genes were calculated for 62 SNPs on 17 human chromosomes for their possible involvement in clearance of drug-resistant parasites with the triple mutations of pfcrt76T, pfmdr86Y, and pfmdr1246Y (TY) and pfdhfr51I, pfdhfr59R, pfdhfr108N, and pfdhps437G (IRNG) which were determined by dotblot or PCRrestriction analysis. Differences in SNP frequencies and association analysis were carried out by comparing Chi-square odds ratios (ORs) and stratified by Mantel-Haenzel statistics. An adjusted P value (OR) ,0.0008 was considered significant. Results: Post-treatment drug failure rates were amodiaquine (36.4%); sulpadoxine/pyrimethamineamodiaquine combination (

BackgroundThe transcription factor 7-like 2 (TCF7L2) is one of the genes that have been identified as possible determinants of diabetes which is associated with obesity. Data on the genetic causes of obesity in sub-Saharan African populations are very scares. The aim of this study was to assess the association between the transcription factor 7-like 2 (TCF7L2) gene polymorphism (rs12255372 G/T) and obesity and weight-related traits in a Cameroonian population.MethodsA case–control study was conducted on 35 obese and 30 non-obese Cameroonian adults. TCF7L2 rs12255372 genotypes were determined using PCR–RFLP and correlated with BMI and weight-related traits.ResultsNo significant association was observed between the rs12255372 T allele (χ2 = 0.0684, p = 0.79) or the TT genotype (χ2 = 0.372, p = 0.54) of the TCF7L2 gene and obesity in the Cameroonian population. However, amongst the weight-related traits, triglycerides were significantly associated with the T risk allele of the TCF7L2 gene (p = 0.012).ConclusionThis study on Cameroonian subjects replicates the absence of association between the TCF7L2 rs12255372 variant and obesity as observed in European and American populations.

BackgroundResistance to anti-malarial drugs is a widespread problem for control programmes for this devastating disease. Molecular tests are available for many anti-malarial drugs and are useful tools for the surveillance of drug resistance. However, the correlation of treatment outcome and molecular tests with particular parasite markers is not perfect, due in part to individuals who are able to clear genotypically drug-resistant parasites. This study aimed to identify molecular markers in the human genome that correlate with the clearance of malaria parasites after drug treatment, despite the drug resistance profile of the protozoan as predicted by molecular approaches.Methods3721 samples from five African countries, which were known to contain genotypically drug resistant parasites, were analysed. These parasites were collected from patients who subsequently failed to clear their infection following drug treatment, as expected, but also from patients who successfully cleared their infections with drug-resistant parasites. 67 human polymorphisms (SNPs) on 17 chromosomes were analysed using Sequenom's mass spectrometry iPLEX gold platform, to identify regions of the human genome, which contribute to enhanced clearance of drug resistant parasites.ResultsAn analysis of all data from the five countries revealed significant associations between the phenotype of ability to clear drug-resistant Plasmodium falciparum infection and human immune response loci common to all populations. Overall, three SNPs showed a significant association with clearance of drug-resistant parasites with odds ratios of 0.76 for SNP rs2706384 (95% CI 0.71-0.92, P = 0.005), 0.66 for SNP rs1805015 (95% CI 0.45-0.97, P = 0.03), and 0.67 for SNP rs1128127 (95% CI 0.45-0.99, P = 0.05), after adjustment for possible confounding factors. The first two SNPs (rs2706384 and rs1805015) are within loci involved in pro-inflammatory (interferon-gamma) and anti-inflammatory (IL-4) cytokine responses. The third locus encodes a protein involved in the degradation of misfolded proteins within the endoplasmic reticulum, and its role, if any, in the clearance phenotype is unclear.ConclusionsThe study showed significant association of three loci in the human genome with the ability of parasite to clear drug-resistant P. falciparum in samples taken from five countries distributed across sub-Saharan Africa. Both SNP rs2706384 and SNP1805015 have previously been reported to be associated with risk of malaria infection in African populations. The loci are involved in the Th1/Th2 balance, and the association of SNPs within these genes suggests a key role for antibody in the clearance of drug-resistant parasites. It is possible that patients able to clear drug-resistant infections have an enhanced ability to control parasite growth.

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.