Prevalence of high-risk human papillomavirus genotypes in outpatient Malian women living with HIV: a pilot study.

INTRODUCTION: Long-term exposure to high-risk human papillomavirus (Hr-HPV) is a well-known necessary condition for development of cervical cancer. The aim of this study is to screen for Hr-HPV using vaginal self-sampling, which is a more effective approach to improve women's adherence and increase screening rates. METHODS: This pilot study included a total of 100 Women living with HIV (WLWHIV), recruited from the Center for Listening, Care, Animation, and Counseling of People Living with HIV in Bamako. Hr-HPV genotyping was performed on Self-collected samples using the Cepheid GeneXpert instrument. RESULTS: The median age of WLWHIV was 44 (interquartile range [IQR], 37-50) years. Approximately 92% of the study participants preferred self-sampling at the clinic, and 90% opted to receive result notifications via mobile phone contact. The overall prevalence of Hr-HPV among study participants was 42.6%, and the most frequent Hr-HPV sub-types observed were HPV18/45 (19.1%), HPV31/35/33/52/58 (13.8%), and HPV39/68/56/66 (12.8%), followed by HPV16 (5.3%), and HPV51/59 (5.3%). WLWHIV under 35 years of age had a higher frequency of Hr-HPV compared to their older counterparts, with rates of 30% versus 11.1% (p = 0.03). The duration of antiretroviral treatment showed an inverse association with Hr-HPV negativity, with patients on treatment for 15 (IQR, 10-18) years versus 12 (IQR = 7-14) years for Hr-HPV positive patients (95% CI [1.2-5.8], t = 3.04, p = 0.003). WLWHIV with baseline CD4 T-Cell counts below 200 exhibited a higher frequency of Hr-HPV compared to those with baseline CD4 T-Cell counts above 200 (17.9% versus 1.9%, p = 0.009). However, other demographics and clinical factors, such as marital status, age of sexual debut, parity, education, history of abortion, history of preeclampsia, and cesarean delivery, did not influence the distribution of Hr-HPV genotypes. CONCLUSION: Our findings indicate that WLWHIV under the age of 35 years old exhibited the highest prevalence of Hr-HPV infection, with HPV18/45 being the most prevalent subtype. Additionally, WLWHIV with baseline CD4 T-Cell counts below 200 showed the highest infection rates.

Lack of Association of C677T Methylenetetrahydrofolate Reductase Polymorphism with Breast Cancer Risk in Mali.

Methylenetetrahydrofolate reductase (MTHFR) plays a major role in the metabolism of folates and homocysteine, which in turn can affect gene expression and ultimately promote the development of breast cancer. Thus, mutations in the MTHFR gene could influence homocysteine, methionine, and S-adenosylmethionine levels and, indirectly, nucleotide levels. Imbalance in methionine and S-adenosylmethionine synthesis affects protein synthesis and methylation. These changes, which affect gene expression, may ultimately promote the development of breast cancer. We therefore hypothesized that such mutations could also play an important role in the occurrence and pathogenesis of breast cancer in a Malian population. In this study, we used the PCR-RFLP technique to identify the different genotypic profiles of the C677T MTHFR polymorphism in 127 breast cancer women and 160 healthy controls. The genotypic distribution of the C677T polymorphism in breast cancer cases was 88.2% for CC, 11.0% for CT, and 0.8% for TT. Healthy controls showed a similar distribution with 90.6% for CC, 8.8% for CT, and 0.6% for TT. We found no statistical association between the C677T polymorphism and breast cancer risk for the codominant models CT and TT (p > 0.05). The same trend was observed when the analysis was extended to other genetic models, including dominant (p = 0.50), recessive (p = 0.87), and additive (p = 0.50) models. The C677T polymorphism of MTHFR gene did not influence the risk of breast cancer in the Malian samples.

Influence of CYP2B6 and CYP3A4 polymorphisms on the virologic and immunologic responses of patients treated with efavirenz-containing regimen.

OBJECTIVES: The main objective of this study was to evaluate the effect of CYP2B6 and CYP3A4 polymorphisms on the virological and immunologic responses of HIV patients. A total of 153 HIV-positive patients were enlisted for the study. PATIENTS AND METHODS: Viral load and median CD4 T cell counts were evaluated at baseline and month 6 (M6). Samples were identified using TaqMan genotyping assays. RESULTS: The AG in CYP2B6 rs2279343 was associated with VLS compared to homozygous AA. In the dominant model, the AG/GG genotypes were associated with VLS compared to the AA genotype. Moreover, in overdominant model, the AG genotype was associated with VLS compared to AA/GG. Regarding immunological response, only the AG in SNP rs2279343 CYP2B6 was associated with an increase in CD4 cell count between baseline and M6. In CYP2B6 rs3745274, the CD4 cell count at M6 was higher than that of baseline for GG carriers and for GT carriers. In CYP3A4 rs2740574, the TC carriers showed a higher median CD4 count at M6 compared to that of the baseline count, as well as for CC carriers. The best genotypes combination associated with CD4 cell count improvement were AA/AG in SNP rs2279343 and GG/GT in SNP rs3745274. CONCLUSION: Our findings support the fact that CYP2B6 rs2279343 could help in the prediction of VLS and both SNPs rs3745274 and rs2279343 in CYP2B6 and CYP3A4 rs2740574 were associated with immune recovery in Malian HIV-positive patients.

Association of the Interleukin-10-592C/A Polymorphism and Cervical Cancer Risk: A Meta-Analysis.

A literature review showed some discrepancies regarding the association of -592C/A with the risk of cervical cancer. To allow more precise analysis of the data by increasing the number of cases studied and more acceptable generalization by considering results from different sources, the present meta-analysis was performed on available published studies that explored the relationship between SNP-592C/A of the IL-10 gene and the risk of cervical cancer. Eleven available studies, including 4187 cases and 3311 controls, were included in this study investigating the relationship between the -592C/A polymorphism of IL-10 and cervical cancer risk. Fixed-effects or random-effects models were performed with pooled odds ratios (ORs). Heterogeneity and bias tests were performed by the inconsistency test and funnel plot, respectively. The overall analysis showed an increased susceptibility to cervical cancer with the -592C/A polymorphism of the IL-10 gene for the recessive model (OR = 1.30, 95% CI = 1.14-1.49), dominant model (OR = 1.36, 95% CI = 1.09-1.70), and additive model (OR = 1.25, 95% CI = 1.09-1.44). Regarding ethnicity, a significant association of the -592C/A polymorphism of the IL-10 gene was linked to an elevated risk of cervical cancer for all genetic models (recessive, dominant, and additive) in the Asian populations and for the recessive and additive models in Caucasians with P < 0.05. The -592C/A polymorphism of the IL-10 gene may be considered a risk factor for cervical cancer.

Descriptive study of cases of schizophrenia in the Malian population.

BACKGROUND: Schizophrenia is a relatively common disease worldwide with a point prevalence of around 5/1000 in the population. The aim of this present work was to assess the demographic, clinical, familial, and environmental factors associated with schizophrenia in Mali. METHODS: This was a prospective descriptive study on a series of 164 patients aged at least 12 years who came for a follow-up consultation at the psychiatry department of the University Hospital Center (CHU) Point G in Mali between February 2019 and January 2020 for schizophrenia spectrum disorder as defined by DSM-5 diagnostic criteria. RESULTS: Our results revealed that the male sex was predominant (80.5%). The 25-34 age group was more represented with 44.5%. The place of birth for the majority of our patients was the urban area (52.4%), which also represented the place of the first year of life for the majority of our patients (56.1%). We noted that the unemployed and single people accounted for 56.1 and 61% respectively. More than half of our patients 58.5% reported having reached secondary school level. With the exception of education level, there was a statistically significant difference in the distribution of demographic parameters. Familial schizophrenia cases accounted for 51.7% versus 49.3% for non-familial cases. The different clinical forms were represented by the paranoid form, followed by the undifferentiated form, and the hebephrenic form with respectively 34, 28 and 17.1%. We noted that almost half (48.8%) of patients were born during the cold season. Cannabis use history was not observed in 68.7% of the patients. The proportions of patients with an out-of-school father or an out-of-school mother were 51.2 and 64.2%, respectively. CONCLUSION: The onset of schizophrenia in the Malian population has been associated with socio-demographic, clinical, genetic and environmental characteristics.

Analysis of the influence of glutathione S-transferase (GSTM1 and GSTT1) genes on the risk of essential hypertension.

BACKGROUND: Essential hypertension (EH) results from a complex interaction between environmental factors and an individual's genetic background. AIM: To assess the relationship between polymorphisms in GSTM1 and GSTT1 and the risk of EH. SUBJECTS AND METHODS: A multiplex-PCR was used to identify the genotypic profiles of GSTM1 and GSTT1 in 160 patients and 210 controls. RESULTS: The frequency of GSTM1-null genotype was higher in patients younger than 61 years when compared to those over 61 years. Interestingly, GSTT1-null was significantly associated with the risk of EH (OR 4; 95% CI 2.6-6.3; p < 0.0001). While GSTM1-null showed no trend (OR 0.7; 95% CI 0.5-1.1, p = 0.12). Individuals carrying the combined GSTT1-null/GSTM1-null were 2.4 times more at risk for hypertension compared to those harbouring the combined GSTT1-present/GSTM1-present genotype (OR 2.4; 95% CI 1.3-4.4; p = 0.005). Additionally, the presence of the combined GSTT1-null/GSTM1-present was associated with an increased risk of EH compared to GSTT1-present/GSTM1-present carriers (OR 6.75; 95% CI 3.4-13.2; p < 0.0001). CONCLUSION: This study showed that the GSTT1-null alone or in interaction with GSTM1-present or GSTM1-null was associated with a higher risk of hypertension. Moreover, the GSTM1-null seems to be associated with the age of onset of hypertension.

p.Arg72Pro polymorphism of P53 and breast cancer risk: a meta-analysis of case-control studies.

BACKGROUND: The effect of the p.Arg72Pro variant of the P53 gene on the risk of development ofbreast cancer remains variable in populations. However, the use ofstrategies such aspoolingage-matched controls with disease may provide a consistent meta-analysis. Our goal was to perform a meta-analysis in order to assess the association of p.Arg72Pro variant of P53 gene with the risk of breast cancer. METHODS: Databases such as PubMed, Genetics Medical Literature, Harvard University Library, Web of Science and Genesis Library were used to search articles. Case-control studies with age-matched on breast cancer havingevaluated the genotype frequencies of the TP53 p.Arg72Pro polymorphism were selected. The fixed and random effects (Mantel-Haenszel) were calculated using pooled odds ratio of 95% CI to determine the risk of disease. Inconsistency was calculated to determine heterogeneity among the studies. The publication bias was estimated using the funnel plot. RESULTS: Twenty-one publications with 7841 cases and 8876 controls were evaluated in this meta-analysis. Overall, our results suggested that TP53 p.Arg72Pro was associated with the risk of breast cancer for the dominant model (OR = 1.09, 95% CI = 1.02-1.16, P = 0.01) and the additive model (OR = 1.09, 95% CI = 1.01-1.17, P = 0.03), but not for the recessive model (OR = 1.07, 95% CI = 0.97-1.18, P = 0.19). According to the ethnic group analysis, Pro allele was associated with the risk of breast cancer in Caucasians for the dominant model and additive model (P = 0.02), and Africans for the recessive model and additive model (P = 0.03). CONCLUSIONS: This meta-analysis found a significant association between TP53 p.Arg72Pro polymorphism and the risk of breast cancer. Individuals carrying at least one Pro allele were more likely to have breast cancer than individuals harboring the Arg allele.

Association of PIN3 16-bp duplication polymorphism of TP53 with breast cancer risk in Mali and a meta-analysis.

BACKGROUND: Breast cancer, the most common tumor in women in Mali and worldwide has been linked to several risk factors, including genetic factors, such as the PIN3 16-bp duplication polymorphism of TP53. The aim of our study was to evaluate the role of the PIN3 16-bp duplication polymorphism in the susceptibility to breast cancer in the Malian population and to perform a meta-analysis to better understand the correlation with data from other populations. METHODS: We analyzed the PIN3 16-bp duplication polymorphism in blood samples of 60 Malian women with breast cancer and 60 healthy Malian women using PCR. In addition, we performed a meta-analysis of case-control study data from international databases, including Pubmed, Harvard University Library, Genetics Medical Literature Database, Genesis Library and Web of Science. Overall, odds ratio (OR) with 95% CI from fixed and random effects models were determined. Inconsistency was used to assess heterogeneity between studies and publication bias was estimated using the funnel plot. RESULTS: In the studied Malian patients, a significant association of PIN3 16-bp duplication polymorphism with breast cancer risk was observed in dominant (A1A2 + A2A2 vs. A1A1: OR = 2.26, CI 95% = 1.08-4.73; P = 0.02) and additive (A2 vs. A1: OR = 1.87, CI 95% = 1.05-3.33; P = 0.03) models, but not in the recessive model (P = 0.38). In the meta-analysis, nineteen (19) articles were included with a total of 6018 disease cases and 4456 controls. Except for the dominant model (P = 0.15), an increased risk of breast cancer was detected with the recessive (OR = 1.46, 95% CI = 1.15-1.85; P = 0.002) and additive (OR = 1.11, 95% CI = 1.02-1.19; P = 0.01) models. CONCLUSION: The case-control study showed that PIN3 16-bp duplication polymorphism of TP53 is a significant risk factor for breast cancer in Malian women. These findings are supported by data from the meta-analysis carried out on different ethnic groups around the world.

Genetic polymorphism of drug metabolism enzymes (GSTM1, GSTT1 and GSTP1) in the healthy Malian population.

Glutathione S-transferase genes, known to be highly polymorphic, are implicated in the process of phase II metabolism of many substrates, including xenobiotics, anticancer and anti-infective drugs. The detoxification activity is linked to individual genetic makeup. Therefore, the identification of alleles and genotypes in these genes within a population may help to better design genetic susceptibility and pharmacogenetic studies. We performed the present study to establish the frequencies of the GSTM1, GSTT1, and GSTP1 c. 313A > G (rs1695) polymorphisms in 206 individuals of the Malian healthy population. GSTM1 and GSTT1 were genotyped by using multiplex polymerase chain reaction, whereas genotypes of GSTP1 were identified by polymerase chain reaction followed by restriction fragment length polymorphism. The frequencies of GSTM1-null and GSTT1-null genotypes were respectively 24.3 and 41.3%. The observed genotype frequencies for GSTP1 were 25.73% homozygous wild-type AA, 49.03% heterozygous AG and 25.24% homozygous mutant GG. The frequency of GSTP1-A allele was 50.24% versus 49.76% for the GSTP1-G allele. The distribution of these three genes was homogeneous between men and women (p > 0.05). We found no statistical association between the presence of a particular profile of GSTM1 or GSTT1 with the genotypes of GSTP1 (p > 0.05). Nevertheless, we noticed that the majority of the individuals harboring the GSTM1-present or the GSTT1-present harbor also the GSTP1-AG genotype. In addition, the triple genotype GSTM1-present/GSTT1-present/AG was the most frequent with 25.2%. Our findings will facilitate future studies regarding genetic associations of multifactorial diseases and pharmacogenetic, thus opening the way to personalized medicine in our population.

Association between ABCB1 C3435T polymorphism and breast cancer risk: a Moroccan case-control study and meta-analysis.

BACKGROUND: Breast cancer is the most common cause of cancer death among women. Several studies have investigated the relationship between the C3435T polymorphism of ABCB1 gene and risk of breast cancer; but the results are conflicting. In the present study, we sought to assess the relationship between the C3435T polymorphism in ABCB1 gene and the risk of breast cancer in a sample of the Moroccan population. METHODS: A case control study was performed on 60 breast cancer patients and 68 healthy women. The ABCB1 C3435T polymorphism was analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Furthermore, a meta-analysis including 16 studies with 6094 cases of breast cancer and 8646 controls was performed. RESULTS: Genotype frequencies were 50 % for CC, 33.3 % for CT and 16.7 % for TT in patients and 41.2 % for CC, 48.5 % for CT and 10.3 % for TT respectively in the control group. This difference was not statistically significant. The same trend as observed in the allele distribution between patients and controls (P = 0.84). Findings from the meta-analysis showed that the ABCB1 C3435T polymorphism was not associated with an increased risk of breast cancer in the dominant model (OR = 0.907; 95 % CI = 0.767-1.073; P = 0.25) as well as in the recessive model (OR = 1.181; 95 % CI = 0.973-1.434; P = 0.093) and in the allele contrast model (OR = 1.098; 95 % CI = 0.972-1.240; P = 0.133). However, the stratification of studies on ethnic basis showed that the TT genotype was associated with the risk of breast cancer in Asians (OR = 1.405; 95 % CI = 1.145-1.725; P = 0.001), Caucasians (OR = 1.093; 95 % CI = 1.001-1.194; P = 0.048) and North African (OR = 2.028; 95 % CI = 1.220-3.371; P = 0.006). CONCLUSIONS: We have noted that the implication of C3435T variant on the risk of breast cancer was ethnicity-dependent. However, there is no evidence that ABCB1 C3435T polymorphism could play a role in susceptibility to breast cancer in Morocco. Further studies with a larger sample size, extended to other polymorphisms are needed to understand the influence of ABCB1 genetic variants on the risk of breast cancer.

Genetic Polymorphisms of Multidrug Resistance Gene-1 (MDR1/ABCB1) and Glutathione S-Transferase Gene and the Risk of Inflammatory Bowel Disease among Moroccan Patients.

Inflammatory bowel diseases (IBD) are multifactorial disorders resulting from environmental and genetic factors. Polymorphisms in MDR1 and GSTs genes might explain individual differences in susceptibility to IBD. We carried out a case-control study to examine the association of MDR1 (C1236T and C3435T), GSTT1, and GSTM1 polymorphisms with the risk of IBD. Subjects were genotyped using PCR-RFLP for MDR1 gene and multiplex PCR for GSTT1 and GSTM1. Meta-analysis was performed to test the association of variant allele carriage with IBD risk. We report that GSTT1 null genotype is significantly associated with the risk of CD (OR: 2.5, CI: 1.2-5, P = 0.013) and UC (OR: 3.5, CI: 1.5-8.5, P = 0.004) and can influence Crohn's disease behavior. The interaction between GSTT1 and GSTM1 genes showed that the combined null genotypes were associated with the risk of UC (OR: 3.1, CI: 1.1-9, P = 0.049). Furthermore, when compared to combined 1236CC/CT genotypes, the 1236TT genotype of MDR1 gene was associated with the risk of UC (OR: 3.7, CI: 1.3-10.7, P = 0.03). Meta-analysis demonstrated significantly higher frequencies of 3435T carriage in IBD patients. Our results show that GSTT1 null and MDR1 polymorphisms could play a role in susceptibility to IBD.

Seasonal variation in metabolic rate, flight activity and body size of Anopheles gambiae in the Sahel.

Malaria in Africa is vectored primarily by the Anopheles gambiae complex. Although the mechanisms of population persistence during the dry season are not yet known, targeting dry season mosquitoes could provide opportunities for vector control. In the Sahel, it appears likely that M-form A. gambiae survive by aestivation (entering a dormant state). To assess the role of eco-physiological changes associated with dry season survival, we measured body size, flight activity and metabolic rate of wild-caught mosquitoes throughout 1 year in a Sahelian locality, far from permanent water sources, and at a riparian location adjacent to the Niger River. We found significant seasonal variation in body size at both the Sahelian and riparian sites, although the magnitude of the variation was greater in the Sahel. For flight activity, significant seasonality was only observed in the Sahel, with increased flight activity in the wet season when compared with that just prior to and throughout the dry season. Whole-organism metabolic rate was affected by numerous biotic and abiotic factors, and a significant seasonal component was found at both locations. However, assay temperature accounted completely for seasonality at the riparian location, while significant seasonal variation remained after accounting for all measured variables in the Sahel. Interestingly, we did not find that mean metabolic rate was lowest during the dry season at either location, contrary to our expectation that mosquitoes would conserve energy and increase longevity by reducing metabolism during this time. These results indicate that mosquitoes may use mechanisms besides reduced metabolic rate to enable survival during the Sahelian dry season.

Relationships between gut microbiota, red meat consumption and colorectal cancer.

Excessive consumption of red and processed meat has been associated with a higher risk of developing colorectal cancer. There are many attempts to explain the risk of colorectal cancer associated with the consumption of red and processed meat: The temperature cooking of meat such as grilling and smoking contribute to the formation of mutagenic compounds including heterocyclic amines and polycyclic aromatic hydrocarbons.Heme iron in red meat is involved in the formation of N-nitroso compounds and lipid peroxidation products in the digestive tract.Fatty red meat is involved in the production of secondary bile acids by the bacteria of the gut microbiota. Many of the products formed are genotoxic and can cause DNA damage and initiate carcinogenesis of colorectal cancer. Various mechanisms contributing to their genotoxic role have been established in human and animal studies. In addition, there is increasing evidence that compounds formed from red and processed meat interact with the gut microbiota in colorectal cancer pathways. Although several early studies in animals and humans suggest a direct causal role of the gut microbiota in the development of colorectal cancer, the links between diet, gut microbiota, and colonic carcinogenesis are largely associations rather than proven causal relationships. Various biological mechanisms, including inflammation and oxidative stress can lead to DNA damage, gut dysbiosis, and therefore increase the risk of colorectal cancer. Dysbiosis of the gut microbiota may increase the risk of colorectal cancer through dietary component promotion of colonic carcinogenesis. In this paper, we review and update current knowledge about the relationships between red meat consumption, gut microbiota, and colorectal cancer.

Variation in metabolic rate of Anopheles gambiae and A. arabiensis in a Sahelian village.

In the Sahel, the Anopheles gambiae complex consists of Anopheles arabiensis and the M and S molecular forms of A. gambiae sensu stricto. However, the composition of these malaria vectors varies spatially and temporally throughout the region and is thought to be linked to environmental factors such as rainfall, larval site characteristics and duration of the dry season. To examine possible physiological divergence between these taxa, we measured metabolic rates of mosquitoes during the wet season in a Sahelian village in Mali. To our knowledge, this study provides the first measurements of metabolic rates of A. gambiae and A. arabiensis in the field. The mean metabolic rate of A. arabiensis was higher than that of M-form A. gambiae when accounting for the effects of female gonotrophic status, temperature and flight activity. However, after accounting for their difference in body size, no significant difference in metabolic rate was found between these two species (whilst all other factors were found to be significant). Thus, body size may be a key character that has diverged in response to ecological differences between these two species. Alternatively, these species may display additional differences in metabolic rate only during the dry season. Overall, our results indicate that changes in behavior and feeding activity provide an effective mechanism for mosquitoes to reduce their metabolic rate, and provide insight into the possible strategies employed by aestivating individuals during the dry season. We hypothesize that female mosquitoes switch to sugar feeding while in dormancy because of elevated metabolism associated with blood digestion.

The contribution of aestivating mosquitoes to the persistence of Anopheles gambiae in the Sahel.

BACKGROUND: Persistence of African anophelines throughout the long dry season (4-8 months) when no surface waters are available remains one of the enduring mysteries of medical entomology. Recent studies demonstrated that aestivation (summer diapause) is one mechanism that allows the African malaria mosquito, Anopheles gambiae, to persist in the Sahel. However, migration from distant localities - where reproduction continues year-round - might also be involved. METHODS: To assess the contribution of aestivating adults to the buildup of populations in the subsequent wet season, two villages subjected to weekly pyrethrum sprays throughout the dry season were compared with two nearby villages, which were only monitored. If aestivating adults are the main source of the subsequent wet-season population, then the subsequent wet-season density in the treated villages will be lower than in the control villages. Moreover, since virtually only M-form An. gambiae are found during the dry season, the reduction should be specific to the M form, whereas no such difference is predicted for S-form An. gambiae or Anopheles arabiensis. On the other hand, if migrants arriving with the first rain are the main source, no differences between treated and control villages are expected across all members of the An. gambiae complex. RESULTS: The wet-season density of the M form in treated villages was 30% lower than that in the control (P < 10-4, permutation test), whereas no significant differences were detected in the S form or An. arabiensis. CONCLUSIONS: These results support the hypothesis that the M form persist in the arid Sahel primarily by aestivation, whereas the S form and An. arabiensis rely on migration from distant locations. Implications for malaria control are discussed.

Distribution of alleles, genotypes and haplotypes of the CYP2B6 (rs3745274; rs2279343) and CYP3A4 (rs2740574) genes in the Malian population: Implication for pharmacogenetics.

ABSTRACT: Cytochrome P450 enzymes play a central role in the phase I biotransformation process of a wide range of compounds, including xenobiotics, drugs, hormones and vitamins. It is noteworthy that these enzymes are highly polymorphic and, depending on the genetic makeup, an individual may have impaired enzymatic activity. Therefore, the identification of genetic variants in these genes could facilitate the implementation of pharmacogenetic studies and genetic predisposition to multifactorial diseases. We have established the frequencies of CYP2B6 (rs3745274; rs2279343) and CYP3A4 (rs2740574) alleles and genotypes in 209 healthy Malian subjects using TaqMan drug metabolism genotyping assays for allelic discrimination. Allele frequencies were 37% for CYP2B6 rs3745274; 38% for CYP2B6 rs2279343; and 75% for CYP3A4 rs2740574 respectively. Overall, the frequencies observed in Mali are statistically comparable to those reported across Africa except North Africa. The major haplotypes in CYP2B6 rs3745274 and CYP2B6 rs2279343 were represented by GA (60.24%) followed by TG (35.36%). We noted a strong linkage disequilibrium between CYP2B6 rs3745274 and CYP2B6 rs2279343 with D' = 0.91 and r2 = 0.9. The frequencies of the genotypic combinations were 43.5% (GT/AG), 37.3% (GG/AA) and 11.5% (TT/GG) in the combination of CYP2B6-rs3745274 and CYP2B6-rs2279343; 26.8% (GT/CC), 25.4%, (GT/CT), 17.2% and GG/CT in the combination CYP2B6-rs3745274-CYP3A4-rs2740574; 26.8% (AG/CC), 23.9% (AA/CC), 19.1% (AG/CT), and 11% (AA/CT) in the combination CYP2B6-rs2279343-CYP3A4-rs2740574, respectively. The most common triple genotype was GT/AG/CC with 24.9%, followed by GG/AA/CC with 23.9%, GT/AG/CT with 16.7%, and GG/AA/CT with 10%. Our results provide new insights into the distribution of these pharmacogenetically relevant genes in the Malian population. Moreover, these data will be useful for studies of individual genetic variability to drugs and genetic predisposition to diseases.

Reproduction-longevity trade-off in Anopheles gambiae (Diptera: Culicidae).

Reduced survival and future reproduction due to of current reproduction is a trade-off known as the cost of reproduction. Surprisingly, only a few studies have assessed the cost of reproduction in arthropod disease vectors, despite its effect on longevity, and thus on vectorial capacity. We evaluated the cost of reproduction on survival of Anopheles gambiae Giles by comparing mosquitoes that were denied exposure to the other sex, hereafter named virgins, and those that were allowed exposure to the other sex and mating, hereafter named mated. Merely 6 d of exposure to females with mating activity reduced male survival from a median of 17 d in virgins to 15 d in mated, indicating that male mating cost is substantial. The increase in mortality of mated males began several days after the exposure to females ended, indicating that mating is not associated with immediate mortality risk. Notably, body size was negatively correlated with male mortality in mated males, but not in virgins. The rate of insemination declined after 4 d of exposure to females, indicating that male mating capacity is limited and further supporting the hypothesis that mating is costly for males. Consistent with previous studies, female survival on sugar alone (median=16 d) was shorter than on blood and sugar (median=19 d), regardless if she was mated or virgin. Overall, survival of mated females was lower than that of virgins on a diet of blood and sugar, but no difference was found on a diet of sugar only. However, the cost of reproduction in females remains ambiguous because the difference in survival between virgin and mated females was driven by the difference between virgin (median=19 d) and uninseminated females exposed to males (median=17 d), rather than between virgin and inseminated females (median=19 d). Accordingly, sperm and seminal fluid, egg development, and oviposition have negligible cost in terms of female survival. Only exposure to males without insemination decreased female survival. Nonetheless, if exposure to males under natural conditions is also associated with reduced survival, it might explain why females remain monogamous.

Prevalence and determinants of breast cancer screening in four sub-Saharan African countries: a population-based study.

OBJECTIVES: Breast cancer is the most prevalent cancer and the second leading cause of cancer-related deaths among women after cervical cancer in much of sub-Saharan Africa. This study aims to examine the prevalence and sociodemographic-socioeconomic factors associated with breast cancer screening among women of reproductive age in sub-Saharan Africa. DESIGN: A weighted population-based cross-sectional study using Demographic and Health Surveys (DHS) data. We used all available data on breast cancer screening from the DHS for four sub-Saharan African countries (Burkina Faso, Ivory Coast, Kenya and Namibia). Breast cancer screening was the outcome of interest for this study. Multivariable Poisson regression was used to identify independent factors associated with breast cancer screening. SETTING: Four countries participating in the DHS from 2010 to 2014 with data on breast cancer screening. PARTICIPANTS: Women of reproductive age 15-49 years (N=39 646). RESULTS: The overall prevalence of breast cancer screening was only 12.9% during the study period, ranging from 5.2% in Ivory Coast to 23.1% in Namibia. Factors associated with breast cancer screening were secondary/higher education with adjusted prevalence ratio (adjusted PR)=2.33 (95% CI: 2.05 to 2.66) compared with no education; older participants, 35-49 years (adjusted PR=1.73, 95% CI : 1.56 to 1.91) compared with younger participants 15-24 years; health insurance coverage (adjusted PR=1.57, 95% CI: 1.47 to 1.68) compared with those with no health insurance and highest socioeconomic status (adjusted PR=1.33, 95% CI : 1.19 to 1.49) compared with lowest socioeconomic status. CONCLUSION: Despite high breast cancer mortality rates in sub-Saharan Africa, the prevalence of breast cancer screening is substantially low and varies gradually across countries and in relation to factors such as education, age, health insurance coverage and household wealth index level. These results highlight the need for increased efforts to improve the uptake of breast cancer screening in sub-Saharan Africa.

Sexual Dimorphism of Metabolomic Profile in Arterial Hypertension.

Metabolomic studies have demonstrated the existence of biological signatures in blood of patients with arterial hypertension, but no study has hitherto reported the sexual dimorphism of these signatures. We compared the plasma metabolomic profiles of 28 individuals (13 women and 15 men) with essential arterial hypertension with those of a healthy control group (18 women and 18 men), using targeted metabolomics. Among the 188 metabolites explored, 152 were accurately measured. Supervised OPLS-DA (orthogonal partial least squares-discriminant analysis) showed good predictive performance for hypertension in both sexes (Q2cum = 0.59 in women and 0.60 in men) with low risk of overfitting (p-value-CV ANOVA = 0.004 in women and men). Seventy-five and 65 discriminant metabolites with a VIP (variable importance for the projection) greater than 1 were evidenced in women and men, respectively. Both sexes showed a considerable increase in phosphatidylcholines, a decrease in C16:0 with an increase in C28:1 lysophosphatidylcholines, an increase in sphingomyelins, as well as an increase of symmetric dimethylarginine (SDMA), acetyl-ornithine and hydroxyproline. Twenty-nine metabolites, involved in phospholipidic and cardiac remodeling, arginine/nitric oxide pathway and antihypertensive and insulin resistance mechanisms, discriminated the metabolic sexual dimorphism of hypertension. Our results highlight the importance of sexual dimorphism in arterial hypertension.

[Multiparametric biochemical analysis revealing an increase of homocysteinemia and NT-proBNP in hypertensive patients living in Bamako (Mali)]. / Analyse biochimique multi-paramétrique révélant une augmentation de l'homocystéinémie et du NT-ProBNP chez les patients hypertendus à Bamako (Mali).

INTRODUCTION: Arterial hypertension is a major public health problem in sub-Saharan Africa due to its high frequency and to the cardiovascular risk that it entails. The purpose of this study was to assess the prevalence of clinical and biological risk factors of hypertension in Bamako (Mali). METHODS: We conducted a case-control study, stratified in function of the sex, of 72 participants including 36 patients with hypertension and 36 controls. Twenty-two plasma biochemical parameters have been measured and analyzed using univariate and multivariate tests. RESULTS: Hyperhomocysteinemia was found in 55.6% of women (p = 0.03) and 100% of men (p = 0.007) with hypertension. High NT-proBNP was also found in 16.7% of women (VIP > 1 in multivariate model) and of men with hypertension (p = 0.00006). A good multivariate predictive model (OPLS-DA) was only obtained in women with high blood pressure, with Q2cum = 0.73, attesting severe sexual dimorphism associated with arterial hypertension. This model involved eight parameters whose plasma concentration was modified (homocysteine, NT-proBNP, potassium, urea, blood glucose, sodium, chlorine and total proteins). CONCLUSION: We registered a significant association between hyperhomocysteinemia and arterial hypertension. Therefore, the assay of homocysteine associated with good management would decrease the risk of cardiovascular diseases while improving the quality of life of hypertensive patients.