In humans, the transient receptor potential vanilloid 1 (TRPV1) gene is activated by exogenous (e.g., high temperatures, irritating compounds such as capsaicin) and endogenous (e.g., endocannabinoids, inflammatory factors, fatty acid metabolites, low pH) stimuli. It has been shown to be involved in several processes including nociception, thermosensation, and energy homeostasis. In this study, we investigated the association between TRPV1 gene variants, sensory perception (to capsaicin and PROP), and body composition (BMI and bioimpedance variables) in human populations. By comparing sequences deposited in worldwide databases, we identified two haplotype blocks (herein referred to as H1 and H2) that show strong stabilizing selection signals (MAF approaching 0.50, Tajima\'s D > +4.5) only in individuals with sub-Saharan African ancestry. We therefore studied the genetic variants of these two regions in 46 volunteers of sub-Saharan descent and 45 Italian volunteers (both sexes). Linear regression analyses showed significant associations between TRPV1 diplotypes and body composition, but not with capsaicin perception. Specifically, in African women carrying the H1-b and H2-b haplotypes, a higher percentage of fat mass and lower extracellular fluid retention was observed, whereas no significant association was found in men. Our results suggest the possible action of sex-driven balancing selection at the non-coding sequences of the TRPV1 gene, with adaptive effects on water balance and lipid deposition.

BACKGROUND: In vitro and in vivo studies have shown that certain cytokines and hormones may play a role in the development and progression of type 2 diabetes (T2D). However, studies on their role in T2D in humans are scarce. We evaluated associations between 11 circulating cytokines and hormones with T2D among a population of sub-Saharan Africans and tested for causal relationships using Mendelian randomization (MR) analyses.
METHODS: We used logistic regression analysis adjusted for age, sex, body mass index, and recruitment country to regress levels of 11 cytokines and hormones (adipsin, leptin, visfatin, PAI-1, GIP, GLP-1, ghrelin, resistin, IL-6, IL-10, IL-1RA) on T2D among Ghanaians, Nigerians, and Kenyans from the Africa America Diabetes Mellitus study including 2276 individuals with T2D and 2790 non-T2D individuals. Similar linear regression models were fitted with homeostatic modelling assessments of insulin sensitivity (HOMA-S) and β-cell function (HOMA-B) as dependent variables among non-T2D individuals (n = 2790). We used 35 genetic variants previously associated with at least one of these 11 cytokines and hormones among non-T2D individuals as instrumental variables in univariable and multivariable MR analyses. Statistical significance was set at 0.0045 (0.05/11 cytokines and hormones).
RESULTS: Circulating GIP and IL-1RA levels were associated with T2D. Nine of the 11 cytokines and hormones (exceptions GLP-1 and IL-6) were associated with HOMA-S, HOMA-B, or both among non-T2D individuals. Two-stage least squares MR analysis provided evidence for a causal effect of GIP and IL-RA on HOMA-S and HOMA-B in multivariable analyses (GIP ~ HOMA-S β =  - 0.67, P-value = 1.88 × 10-6 and HOMA-B β = 0.59, P-value = 1.88 × 10-5; IL-1RA ~ HOMA-S β =  - 0.51, P-value = 8.49 × 10-5 and HOMA-B β = 0.48, P-value = 5.71 × 10-4). IL-RA was partly mediated via BMI (30-34%), but GIP was not. Inverse variance weighted MR analysis provided evidence for a causal effect of adipsin on T2D (multivariable OR = 1.83, P-value = 9.79 × 10-6), though these associations were not consistent in all sensitivity analyses.
CONCLUSIONS: The findings of this comprehensive MR analysis indicate that circulating GIP and IL-1RA levels are causal for reduced insulin sensitivity and increased β-cell function. GIP\'s effect being independent of BMI suggests that circulating levels of GIP could be a promising early biomarker for T2D risk. Our MR analyses do not provide conclusive evidence for a causal role of other circulating cytokines in T2D among sub-Saharan Africans.

BACKGROUND: Left ventricular hypertrophy (LVH) is associated with impaired cardiorespiratory fitness (CRF), a surrogate marker of poor outcome. Insulin resistance (IR) plays a central role in all stages of cardiovascular disease continuum. This study evaluates IR-related differences in the relationship between left ventricular mass (LVM) and CRF in asymptomatic newly diagnosed hypertensive Black sub-Saharan Africans.
METHODS: In this cross-sectional observational study, 126 asymptomatic newly diagnosed hypertensive participants (50.5 ± 9.5 years) underwent comprehensive resting transthoracic echocardiographic examination and maximal incremental cardiopulmonary exercise test (CPET). CRF was estimated in maximal oxygen uptake (VO2max). CPET results were compared between participants with and without LVH. Multivariate analysis examined the influence of IR on the observed differences.
RESULTS: Those with LVH had lower VO2max (15.7 ± 5.5 mL min-1 kg-1 vs. 18.4 ± 3.7 mL min-1 kg-1; P = 0.001) than those without LVH. In patients with IR, LVM (r = -0.261, P = 0.012), LVM indexed to body surface area (LVMIbsa; r = -0.229, P = 0.027), and LVM indexed to height to an allometric power of 2.7 (LVMIh2.7; r = -0.351, P = 0.001), and VO2max were negatively correlated. In hypertensive patients without IR, these same parameters and VO2max have no significant correlation. Body mass index (BMI), LVM, and LVMIbsa emerged as independent determinants of VO2max, explaining 46.9% of its variability (overall P = 0.001) in IR participants, a relationship not found in participants without IR.
CONCLUSIONS: IR may participate in the deterioration of CRF associated with LVH. Measures to improve insulin sensitivity should be considered for improving CRF and therefore the prognosis of insulin-resistant hypertensive patients. Targeting IR in hypertensive patients with LVH could improve prognosis.

Nonsyndromic cleft lip and/or cleft palate (NSCL/P) have multifactorial etiology where genetic factors, gene-environment interactions, stochastic factors, gene-gene interactions, and parent-of-origin effects (POEs) play cardinal roles. POEs arise when the parental origin of alleles differentially impacts the phenotype of the offspring. The aim of this study was to identify POEs that can increase risk for NSCL/P in humans using a genome-wide dataset.
The samples (174 case-parent trios from Ghana, Ethiopia, and Nigeria) included in this study were from the African only genome wide association studies (GWAS) that was published in 2019. Genotyping of individual DNA using over 2 million multiethnic and African ancestry-specific single-nucleotide polymorphisms from the Illumina Multi-Ethnic Genotyping Array v2 15070954 A2 (genome build GRCh37/hg19) was done at the Center for Inherited Diseases Research. After quality control checks, PLINK was employed to carry out POE analysis employing the pooled subphenotypes of NSCL/P.
We observed possible hints of POEs at a cluster of genes at a 1 mega base pair window at the major histocompatibility complex class 1 locus on chromosome 6, as well as at other loci encompassing candidate genes such as ASB18, ANKEF1, AGAP1, GABRD, HHAT, CCT7, DNMT3A, EPHA7, FOXO3, lncRNAs, microRNA, antisense RNAs, ZNRD1, ZFAT, and ZBTB16.
Findings from our study suggest that some loci may increase the risk for NSCL/P through POEs. Additional studies are required to confirm these suggestive loci in NSCL/P etiology.

Aim: We assessed epigenome-wide DNA methylation (DNAm) differences between migrant and non-migrant Ghanaians. Materials & methods: We used the Illumina Infinium® HumanMethylation450 BeadChip to profile DNAm of 712 Ghanaians in whole blood. We used linear models to detect differentially methylated positions (DMPs) associated with migration. We performed multiple post hoc analyses to validate our findings. Results: We identified 13 DMPs associated with migration (delta-beta values: 0.2-4.5%). Seven DMPs in CPLX2, EIF4E3, MEF2D, TLX3, ST8SIA1, ANG and CHRM3 were independent of extrinsic genomic influences in public databases. Two DMPs in NLRC5 were associated with duration of stay in Europe among migrants. All DMPs were biologically linked to migration-related factors. Conclusion: Our findings provide the first insights into DNAm differences between migrants and non-migrants.

Our study seeks to examine how chronic health status, insurance coverage and socioeconomic factors predict unmet traditional, complementary and alternative medicine (TCAM) needs among immigrants from sub-Saharan African origin living in the Greater Toronto Area (GTA). The data for the study comes from a cross-sectional questionnaire survey of 273 sub-Saharan African immigrants living in the GTA. ~ 21% of respondents surveyed had unmet TCAM needs in the 12-month period prior to the survey. Persons with chronic health conditions, lower socioeconomic status, and those with previous history of TCAM use before immigrating were more likely to have unmet TCAM need. The study suggests that the current TCAM healthcare environment in the GTA limits that ability of sub-Saharan immigrants to meet their healthcare needs, especially persons in most need of such treatments-persons with chronic health conditions and those of lower socioeconomic background.

In the advent of rapid urbanisation, migration and epidemiological transition, the extent to which serum uric acid (sUA) affects cardiovascular disease (CVD) risk among Africans is not well understood. We assessed differences in sUA levels and associations with CVD risk among migrant Ghanaians in Europe and non-migrant Ghanaians in rural and urban Ghana.
Baseline data from 633 rural, 916 urban and 2315 migrant participants (40-70 years) from the cross-sectional RODAM study were analysed. Hyperuricaemia was defined as sUA >7 mg/dl in men and >6 mg/dl in women. The 10-year risk of atherosclerotic cardiovascular disease (ASCVD) was calculated using the American College of Cardiology (ACC)/American Heart Association (AHA) risk score which takes into account ethnic minority populations. High CVD risk was defined as ASCVD risk scores ≥7.5%. Logistic regressions were used to assess associations between hyperuricaemia and CVD risk.
Prevalence for hyperuricaemia in rural, urban and migrant participants was 17.4%, 19.1% and 31.7% for men, and 15.9%, 18.2% and 33.2% for women, respectively. Hyperuricaemia was positively associated with elevated CVD risk among rural residents (adjusted OR for men 3.28, 95% CI: 1.21-8.96, 6.36, 95% CI: 2.98-13.56 for women), urban residents (1.12, 95% CI: 0.45-2.81 for men, 2.11, 95% CI: 1.26-3.52 for women) and migrants (1.73, 95% CI: 1.01-2.96 for men, 4.61, 95% CI: 3.05-6.97 for women).
Our study shows variations of sUA levels in different African contexts. Hyperuricaemia is associated with elevated 10-year CVD risk in both migrants and non-migrants. Further studies should identify factors driving associations between sUA and CVD risk in Africans.
Avec l\'avènement de l\'urbanisation rapide, de la migration et de la transition épidémiologique, la mesure dans laquelle l\'acide urique sérique (AUs) affecte le risque de maladie cardiovasculaire (MCV) chez les Africains n\'est pas bien comprise. Nous avons évalué les différences dans les niveaux d\'AUs et les associations avec le risque de MCV chez les ghanéens migrants en Europe et non migrants dans les zones rurales et urbaines du Ghana. MÉTHODES: Les données de base de 633 participants ruraux, 916 urbains et 2.315 migrants, de 40 à 70 ans de l\'étude transversale RODAM ont été analysées. L\'hyperuricémie a été définie comme une AUs > 7 mg/dl chez les hommes et >6 mg/dl chez les femmes. Le risque sur 10 ans de MCV athérosclérosique (MCVAS) a été calculé en utilisant le score de risque de l\'American College of Cardiology (ACC)/American Heart Association (AHA) qui prend en compte les populations des minorités ethniques. Un risque de MCV élevé était défini comme un score de risque MCVAS ≥7,5%. Des régressions logistiques ont été utilisées pour évaluer les associations entre l\'hyperuricémie et le risque de MCV. RÉSULTATS: La prévalence de l\'hyperuricémie chez les participants ruraux, urbains et migrants était de 17,4% ; 19,1% et 31,7% pour les hommes et 15,9%, 18,2% et 33,2% pour les femmes, respectivement. L\'hyperuricémie était positivement associée à un risque élevé de MCV chez les résidents ruraux (OR ajusté 3,28 ; IC95%: 1,21-8,96 pour les hommes, 6,36, IC95%: 2,98-13,56 pour les femmes), les résidents urbains (1,12 ; IC95%: 0,45-2,81 pour les hommes, 2,11 ; IC95%: 1,26-3,52 pour les femmes) et les migrants (1,73 ; IC95%: 1,01-2,96 pour les hommes, 4,61 ; IC95%: 3,05-6,97 pour les femmes).
Notre étude montre des variations des niveaux d\'AUs dans différents contextes africains. L\'hyperuricémie est associée à un risque élevé de MCV sur 10 ans chez les migrants et les non-migrants. Des études plus poussées devraient identifier les facteurs à l\'origine des associations entre le risque d\'AUs et de MCV chez les africains.

Late presentation (LP) to HIV care disproportionally affects individuals from sub-Saharan Africa (SSA). We explored the reasons for late presentation to care among this group of patients in the Swiss HIV Cohort Study.
The prevalence of LP was compared between patients from Western Europe (WE) and those from SSA enrolled between 2009 and 2012. Patients were asked about HIV testing, including access to testing and reasons for deferring it, during face-to-face interviews.
The proportion of LP was 45.8% (435/950) among patients from WE, and 64.6% (126/195) among those from SSA (P < 0.001). Women from WE were slightly more likely to present late than men (52.6% versus 44.5%, respectively; P = 0.06), whereas there was no sex difference in patients from SSA (65.6% versus 63.2%, respectively; P = 0.73). Compared with late presenters from WE, those from SSA were more likely to be diagnosed during pregnancy (9.1% versus 0%, respectively; P < 0.001), but less likely to be tested by general practitioners (25.0% versus 44.6%, respectively; P = 0.001). Late presenters from SSA more frequently reported \'not knowing about anonymous testing possibilities\' (46.4% versus 27.3%, respectively; P = 0.04) and \'fear about negative reaction in relatives\' (39.3% versus 21.7%, respectively; P = 0.05) as reasons for late testing. Fear of being expelled from Switzerland was reported by 26.1% of late presenters from SSA.
The majority of patients from SSA were late presenters, independent of sex or education level. Difficulties in accessing testing facilities, lack of knowledge about HIV testing and fear-related issues are important drivers for LP in this population.

Psychosocial stress could be an underlying factor for emerging risk of cardiovascular diseases (CVD) in Africans. We assessed the association between psychosocial stress and estimated CVD risk among non-migrant Ghanaians and migrant Ghanaians living in Europe.
Data from the Research on Obesity and Diabetes among African Migrants (RODAM) study, involving 2315 migrant and 1549 non-migrants aged 40-70 years were used for this study. Psychosocial stress included self-reported stress at work and home, recent negative life events and perceived discrimination. CVD risk was estimated using the pooled cohort equations with estimates ≥7.5% over 10 years defining high CVD risk. Adjusted Odds Ratios (AOR) and 95% confidence intervals (95% CI) were calculated by logistic regression with adjustments for socioeconomic status.
Prevalence for migrant and non-migrants were; 72.5% and 84.9% for psychosocial stress and 35.9% and 27.4% for high estimated CVD risk. Stress at work and home was not associated with a high estimated CVD risk in either group. Recent negative life events were associated with a high estimated CVD risk in non-migrants only (AOR 1.29, 95%CI 1.02-1.68, p = 0.048). Higher levels of perceived discrimination were associated with a high estimated CVD risk in migrants only (AOR 2.74, 95%CI 1.95-3.86, p < 0.001).
Among migrant populations, higher levels of perceived discrimination were associated with a high estimated CVD risk, and this was also true for recent negative life events among non-migrant populations. Further research is needed to identify context specific mechanisms that underlie associations between psychological characteristics and CVD risk.

The five closely linked CD1A-E genes encode the human CD1 family of proteins. Few studies of the allele frequencies of these genes in African populations have been published so far. This study aimed to genotype CD1A and CD1E variants and to compare their frequencies in Sub-Saharan Africans from Gabon and Ivory Coast, and Non-Africans from Syria and France. A restriction analysis of DNA fragments generated by PCR was performed to detect CD1A and CD1E alleles in 105 subjects from Gabon, 169 subjects from Ivory Coast, 107 subjects from Syria and 181 subjects from France. The frequencies of the CD1E*02 allele were high among Sub-Saharan Africans (87%) and low in West Asians (44%) and Europeans (36%), whereas the contrary was obtained for the CD1E*01 allele (7%, 55% and 64% respectively). Frequencies of CD1A alleles were similar between all groups, the CD1A*02 allele was most prevalent (91%). The high frequency of the CD1E*02 allele in Sub-Saharan Africans suggest that future work should investigate the relationship between CD1 polymorphism and infectious diseases.