Drug resistance markers within an evolving efficacy of anti-malarial drugs in Cameroon: a systematic review and meta-analysis (1998-2020).

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.

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

OBJECTIVE: This study aimed at investigating the association between the rs7903146 (C/T) polymorphism of the TCF7L2 gene with obesity in a Cameroonian population. METHOD: This 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. RESULTS: The 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. CONCLUSION: The rs7903146 (C/T) polymorphism of the TCF7L2 gene might not be associated with obesity in the Cameroonian population.

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

BACKGROUND: Peroxisome 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. METHODS: This 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). RESULTS: A 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. CONCLUSION: PPAR-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.

Association between the rs12255372 variant of the TCF7L2 gene and obesity in a Cameroonian population.

BACKGROUND: The 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. METHODS: A 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. RESULTS: No significant association was observed between the rs12255372 T allele (χ(2) = 0.0684, p = 0.79) or the TT genotype (χ(2) = 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). CONCLUSION: This study on Cameroonian subjects replicates the absence of association between the TCF7L2 rs12255372 variant and obesity as observed in European and American populations.

Association between the TCF7L2 rs12255372 (G/T) gene polymorphism and type 2 diabetes mellitus in a Cameroonian population: a pilot study.

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.

Contribution of the TCF7L2 rs7903146 (C/T) gene polymorphism to the susceptibility to type 2 diabetes mellitus in Cameroon.

BACKGROUND: Data 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. METHODS: This 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. RESULTS: TCF7L2 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. CONCLUSION: TCF7L2 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.