Polygenic risk score comparator (PRScomp): Test population vs. worldwide populations.

BACKGROUND: Polygenic risk scores (PRS) are a powerful tool for predicting an individual's genetic risk for complex diseases. METHODS: We have developed a web service (PRScomp) as a user-friendly tool to evaluate PRS of the user own population and compare it with worldwide populations. RESULTS: A disease/trait database has been constructed from GWAS Catalog summary statistics. Genotype data of test population is uploaded and merged with the reference dataset (1000 Genome Project and Human Genome Diversity Project) to obtain a file including the common SNPs. The user can select a disease/trait from the database and a curated set of risk markers is used to calculate summatory PRS. Distribution of z-scored PRS values is presented in publication-ready plots and text files that can be downloaded. DISCUSSION: PRScomp can be useful for public health decision-making by identifying population-specific genetic risk factors and informing the development of targeted interventions for at-risk populations.

The power of geohistorical boundaries for modeling the genetic background of human populations: The case of the rural catalan Pyrenees.

The genetic variation of the European population at a macro-geographic scale follows genetic gradients which reflect main migration events. However, less is known about factors affecting mating patterns at a micro-geographic scale. In this study we have analyzed 726,718 autosomal single nucleotide variants in 435 individuals from the catalan Pyrenees covering around 200 km of a vast and abrupt region in the north of the Iberian Peninsula, for which we have information about the geographic origin of all grand-parents and parents. At a macro-geographic scale, our analyses recapitulate the genetic gradient observed in Spain. However, we also identified the presence of micro-population substructure among the sampled individuals. Such micro-population substructure does not correlate with geographic barriers such as the expected by the orography of the considered region, but by the bishoprics present in the covered geographic area. These results support that, on top of main human migrations, long ongoing socio-cultural factors have also shaped the genetic diversity observed at rural populations.

Incidence of COVID-19 in patients exposed to chloroquine and hydroxychloroquine: results from a population-based prospective cohort in Catalonia, Spain, 2020.

BackgroundSeveral clinical trials have assessed the protective potential of chloroquine and hydroxychloroquine. Chronic exposure to such drugs might lower the risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or severe coronavirus disease (COVID-19).AimTo assess COVID-19 incidence and risk of hospitalisation in a cohort of patients chronically taking chloroquine/hydroxychloroquine.MethodsWe used linked health administration databases to follow a cohort of patients with chronic prescription of hydroxychloroquine/chloroquine and a control cohort matched by age, sex and primary care service area, between 1 January and 30 April 2020. COVID-19 cases were identified using International Classification of Diseases 10 codes.ResultsWe analysed a cohort of 6,746 patients (80% female) with active prescriptions for hydroxychloroquine/chloroquine, and 13,492 controls. During follow-up, there were 97 (1.4%) COVID-19 cases in the exposed cohort and 183 (1.4%) among controls. The incidence rate was very similar between the two groups (12.05 vs 11.35 cases/100,000 person-days). The exposed cohort was not at lower risk of infection compared with controls (hazard ratio (HR): 1.08; 95% confidence interval (CI): 0.83-1.44; p = 0.50). Forty cases (0.6%) were admitted to hospital in the exposed cohort and 50 (0.4%) in the control cohort, suggesting a higher hospitalisation rate in the former, though differences were not confirmed after adjustment (HR: 1·46; 95% CI: 0.91-2.34; p = 0.10).ConclusionsPatients chronically exposed to chloroquine/hydroxychloroquine did not differ in risk of COVID-19 nor hospitalisation, compared with controls. As controls were mainly female, findings might not be generalisable to a male population.

Oferta de la prueba del VIH en fluido oral en actividades de acercamiento y consulta de los resultados online: intervención piloto en Cataluña / Outreach HIV testing using oral fluid and online consultation of the results: Pilot intervention in Catalonia

INTRODUCCIÓN: El objetivo de la intervención fue describir la viabilidad y la rentabilidad de la oferta de la prueba del VIH en intervenciones de acercamiento (outreach) y posterior consulta de los resultados a través de una página web segura. MÉTODOS: Se ofreció la autotoma de muestra «in situ» para detección del VIH en fluido oral a hombres que tienen sexo con hombres (HSH), trabajadores/as sexuales migrantes y mujeres trans reclutados en lugares de ocio y sexo. Cuatro ONG colaboradoras reclutaron a las personas participantes y les asistieron para que se dieran de alta en la web del estudio (www.swab2know.eu) a través de una tablet o el smartphone del mismo participante. Las muestras se enviaron al laboratorio de referencia y los resultados se publicaron en la página web. RESULTADOS: Se reclutó a 834 participantes (612 HSH, 203 mujeres trabajadoras sexuales y 19 mujeres trans). En total se detectaron 22 resultados reactivos (2,6%): 21 entre los HSH (3,4%) y uno en una mujer trans (5,3%). Mientras que el 82,6% de los HSH consultó su resultado, solamente el 39,9 y el 26,3% de las mujeres trabajadoras sexuales y las mujeres trans, respectivamente, consultaron su resultado. CONCLUSIONES: Ofrecer la autotoma de muestra en actividades de acercamiento, el envío y el análisis en un laboratorio de referencia y la posterior consulta de los resultados online es viable. Se detectó un elevado porcentaje de usuarios con un resultado reactivo para el VIH entre los HSH y las mujeres trans

INTRODUCTION: The aim of the intervention was to describe the feasibility and cost-effectiveness of offering HIV testing in outreach interventions and subsequent consultation of the results through a secure web page. METHODS: The HIV test was offered "in situ" to men who have sex with men (MSM), migrant sex workers and trans women recruited in places of leisure and sex. Four collaborating NGOs recruited the participants and assisted them to register on the study website (www.swab2know.eu) through a tablet or the smartphone of the same participant. The samples were sent to the reference laboratory and the results were published on the website. RESULTS: 834 participants (612 MSMs, 203 women sex workers and 19 trans women) were recruited. In total 22 reagent results (2.6%) were detected: 21 among MSMs (3.4%) and 1 in a trans women (5.3%). While 82.6% of MSMs consulted their outcome, only 39.9% and 26.3% of women sex workers and trans women respectively consulted their outcome CONCLUSIONS: Providing self-sampling in outreach activities, dispatch and analysis in a reference laboratory as well as online communication of test results is feasible. A high proportion of participants with a HIV reactive result were detected among MSMs and trans women

Outreach HIV testing using oral fluid and online consultation of the results: Pilot intervention in Catalonia. / Oferta de la prueba del VIH en fluido oral en actividades de acercamiento y consulta de los resultados online: intervención piloto en Cataluña.

INTRODUCTION: The aim of the intervention was to describe the feasibility and cost-effectiveness of offering HIV testing in outreach interventions and subsequent consultation of the results through a secure web page. METHODS: The HIV test was offered "in situ" to men who have sex with men (MSM), migrant sex workers and trans women recruited in places of leisure and sex. Four collaborating NGOs recruited the participants and assisted them to register on the study website (www.swab2know.eu) through a tablet or the smartphone of the same participant. The samples were sent to the reference laboratory and the results were published on the website. RESULTS: 834 participants (612 MSMs, 203 women sex workers and 19 trans women) were recruited. In total 22 reagent results (2.6%) were detected: 21 among MSMs (3.4%) and 1 in a trans women (5.3%). While 82.6% of MSMs consulted their outcome, only 39.9% and 26.3% of women sex workers and trans women respectively consulted their outcome CONCLUSIONS: Providing self-sampling in outreach activities, dispatch and analysis in a reference laboratory as well as online communication of test results is feasible. A high proportion of participants with a HIV reactive result were detected among MSMs and trans women.

Lack of protective effect of chloroquine derivatives on COVID-19 disease in a Spanish sample of chronically treated patients.

BACKGROUND: The search for a SARS-CoV-2 treatment has emerged as a worldwide priority. We evaluated the role of chloroquine and its derivatives in COVID-19 in Spanish individuals. METHODS: We performed a survey addressed to patients regularly taking chloroquine and its derivatives for the control of their autoimmune diseases. The survey was distributed with special attention to Spanish patient associations centred on autoimmune diseases and rheumatology and to the general population. A sample of untreated subjects was matched to the treated group according to sex, age range and incidence region. COVID-19 disease prevalence was compared between treated and untreated-matched control sample. RESULTS: A total of 319 surveys of patients regularly taking chloroquine and its derivatives were recovered for further analysis. The prevalence of declared COVID-19 status in the treated group was 5.3% and the mean prevalence among the untreated-matched groups was 3.4%. A community exposition to COVID-19 was associated with a greater prevalence of COVID-19 in both, treated (17.0% vs. 3.2%; p-value<0.001) and untreated groups (13.4% vs. 1.1%; p-value = 0.027). CONCLUSION: We did not find differences of reported COVID-19 cases between treated and untreated groups, indicating a lack of protection by regular administration of chloroquine and its derivative drugs on COVID-19 infection. Of relevance, data indicates that patients that regularly take chloroquine derivatives are exposed to SARS-CoV-2 infection and must take the same protection measures as the general population.

Toll-Like Receptor 2 Promoter -196 to -174 Deletion Affects CD4 Levels Along Human Immunodeficiency Virus Infection Progression.

Toll-like receptor 2 (TLR2) plays a key role in innate immune response recognizing molecular patterns expressed by pathogens. rs111200466 is a TLR2 promoter insertion/deletion polymorphism with contradictory data about its role in human immunodeficiency virus type 1 (HIV-1) infection. We analyzed rs111200466 in HIV-1 disease progression and showed a correlation with a faster progression to the CD4+ < 200 cells/µL outcome for deletion allele carriers (Cox regression analysis: hazard ratio, 2.4 [95% confidence interval, 1.4-4]; P = .001). When naive patients with CD4+ < 200 cells/µL started antiretroviral treatment, rs111200466-deletion carriers showed a trend toward a slower, recovery rate (time required to reach CD4+ > 350 cells/µL; Cox P = .36). Our data suggest rs111200466 as a prognosis factor for HIV-1 disease progression.

Genetic associations of the vitamin D and antiviral pathways with natural resistance to HIV-1 infection are influenced by interpopulation variability.

Vitamin D (VitD) may modulate anti-HIV-1 responses modifying the risk to acquire the HIV-1-infection. We performed a nested case-control exploratory study involving 413 individuals; HIV-1-exposed seropositives (cases) and seronegatives (HESN) (controls) from three cohorts: sexually-exposed from Colombia and Italy and parenterally-exposed from Spain. The association and interactions of 139 variants in 9 VitD pathway genes, and in 14 antiviral genes with resistance/susceptibility (R/S) to HIV-1 infection was evaluated. Associations between variants and mRNA levels were also analyzed in the Colombian samples. Variants and haplotypes in genes of VitD and antiviral pathways were associated with R/S, but specific associations were not reproduced in all cohorts. Allelic heterogeneity could explain such inconsistency since the associations found in all cohorts were consistently in the same genes: VDR and RXRA of the VitD pathway genes and in TLR2 and RNASE4. Remarkably, the multi-locus genotypes (interacting variants) observed in genes of VitD and antiviral pathways were present in most HESNs of all cohorts. Finally, HESNs carrying resistance-associated variants had higher levels of VitD in plasma, of VDR mRNA in blood cells, and of ELAFIN and defensins mRNA in the oral mucosa. In conclusion, despite allelic heterogeneity, most likely due to differences in the genetic history of the populations, the associations were locus dependent suggesting that genes of the VitD pathway might act in concert with antiviral genes modulating the resistance phenotype of the HESNs. Although these associations were significant after permutation test, only haplotype results remained statistically significant after Bonferroni test, requiring further replications in larger cohorts and functional analyzes to validate these conclusions.

Vitamin D Receptor polymorphisms and risk of enveloped virus infection: A meta-analysis.

INTRODUCTION: Vitamin-D plays a role regulating the immune response against to viral infection. In this sense, vitamin-D deficiency may confer increased susceptibility to enveloped virus infection such as HIV, Hepatitis, Dengue and Respiratory Syncytial virus infection, among others. Vitamin D activity is mediated by its receptor (VDR), which acts as a transcription factor modulating the expression of genes triggering the response against viruses. To date, six major VDR polymorphisms (Cdx, A1012G, FokI, BsmI, ApaI and TaqI) have been studied in the context of viral infection susceptibility. Reported studies show controversial results probably due to statistical lack of power and population genetic differences. AIMS: To do a systematic review of the published data and to perform a meta-analysis examining the role of six VDR polymorphisms on infection susceptibility to enveloped virus. RESULTS: From all markers and virus considered an association of FokI polymorphism with RSV infection emerges as significant. The worldwide distribution of risk T-allele reveals a lower prevalence in African populations that runs parallel with the relative lower incidence of RSV-associated severe ALRI in children <1 year described in African samples. CONCLUSION: The results disclose FokI polymorphism as a relevant variant capturing the association of VDR polymorphisms with viral infection.

A common copy-number variant within SIRPB1 correlates with human Out-of-Africa migration after genetic drift correction.

Previous reports have proposed that personality may have played a role on human Out-Of-Africa migration, pinpointing some genetic variants that were positively selected in the migrating populations. In this work, we discuss the role of a common copy-number variant within the SIRPB1 gene, recently associated with impulsive behavior, in the human Out-Of-Africa migration. With the analysis of the variant distribution across forty-two different populations, we found that the SIRPB1 haplotype containing duplicated allele significantly correlated with human migratory distance, being one of the few examples of positively selected loci found across the human world colonization. Circular Chromosome Conformation Capture (4C-seq) experiments from the SIRPB1 promoter revealed important 3D modifications in the locus depending on the presence or absence of the duplication variant. In addition, a 3' enhancer showed neural activity in transgenic models, suggesting that the presence of the CNV may compromise the expression of SIRPB1 in the central nervous system, paving the way to construct a molecular explanation of the SIRPB1 variants role in human migration.

Differential metabolic profiles associated to movement behaviour of stream-resident brown trout (Salmo trutta).

The mechanisms that can contribute in the fish movement strategies and the associated behaviour can be complex and related to the physiology, genetic and ecology of each species. In the case of the brown trout (Salmo trutta), in recent research works, individual differences in mobility have been observed in a population living in a high mountain river reach (Pyrenees, NE Spain). The population is mostly sedentary but a small percentage of individuals exhibit a mobile behavior, mainly upstream movements. Metabolomics can reflect changes in the physiological process and can determine different profiles depending on behaviour. Here, a non-targeted metabolomics approach was used to find possible changes in the blood metabolomic profile of S. trutta related to its movement behaviour, using a minimally invasive sampling. Results showed a differentiation in the metabolomic profiles of the trouts and different level concentrations of some metabolites (e.g. cortisol) according to the home range classification (pattern of movements: sedentary or mobile). The change in metabolomic profiles can generally occur during the upstream movement and probably reflects the changes in metabolite profile from the non-mobile season to mobile season. This study reveals the contribution of the metabolomic analyses to better understand the behaviour of organisms.

Common haplotypes in CD209 promoter and susceptibility to HIV-1 infection in intravenous drug users.

INTRODUCTION: CD209 is a receptor expressed in the dendritic cells involved in recognition of oligosaccharides present in several pathogens with a relevant impact on human health. SNPs located in the promoter region have been associated with HIV-1 susceptibility, although this finding has not been replicated in other populations. The objective of this study is to evaluate the association of CD209 promoter haplotypes with risk of HIV-1 infection in a cohort of Spanish male intravenous drug users (IDU) infected with hepatitis C virus (HCV) and to characterize the phenotypic effects of the associated variants. METHODS: We genotyped 4 SNPs of CD209 promoter in 295 HCV males exposed to HIV-1 infection by IDU, 165 HIV-1-infected and 130 exposed uninfected (EUI) and 142 healthy controls (HC). We have cloned the promoter variants in a reporter vector and evaluated the promoter activities in a cell culture model. CD209 mRNAs were measured in PBMC. RESULTS: Single-marker analysis revealed no significant allelic association with the risk of HIV-1 infection by parenteral route. Nevertheless, one haplotype was significantly overrepresented in EUI compared with HIV-1 positive patients and was associated with HIV-1 status (P=0.0008; OR: 0.43). Functional experiments suggested that the protective haplotype displayed lower transcriptional activity in vitro (P<0.05) and this was correlated with lower CD209 mRNA expression in PBMC (P=0.014). CONCLUSIONS: This study suggests that the promoter haplotypes of CD209 influence the risk of HIV-1 acquisition in IDU and that this association is correlated with the mRNA expression level.

IFNL4 rs368234815 polymorphism is associated with innate resistance to HIV-1 infection.

The interferon (IFN)L4 polymorphism rs368234815 is associated with hepatitis C virus (HCV) spontaneous clearance and response to IFN-based treatments. The role of this polymorphism in HIV-1 infection is controversial. We investigated whether genetic variation at IFNL4 is associated to HIV-1 acquisition. The HCV protective allele TT was associated with decreased likelihood of HIV-1 infection in male intravenous drug users [odds ratio (OR): 0.3; P = 0.006], and this association was not modified by the genotype of CCR5. These results suggest that genetic susceptibility to HCV and HIV-1 infection shares common molecular pathways.

Genotyping of common SIRPB1 copy number variant using Paralogue Ratio Test coupled to MALDI-MS quantification.

Copy number variant (CNV) regions have been proven to have a significant impact on gene expression. Some of them have been also found to be associated to different human diseases. CNV genotyping is often prone to error and cross-validation with independent methods is frequently required. The platform of choice depends on whether it is a genome-wide discovery screening or a candidate CNV study, the cohort size and the number of CNVs included in the assay and, finally, the budget available. Here we illustrate a affordable approach to determine the CNV genotype using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) and based on the quantitative determination of single nucleotide duplicated mismatches (SNDM) mapping the CNV region and a paralogue genomic region that is used as a two-copy reference. We have genotyped nsv436327, a common CNV mapping SIRPB1 intron 1 that has been associated to human personality behavior. SIRP cluster region was subjected to several ancestral duplication events what makes SIRPB1 CNV genotyping technically challenging. We designed three sets of primer pairs that amplified paralogue regions inside and outside the CNV, containing three SNDMs. Post-PCR extension analyses of sequencing oligonucleotides mapping immediately upstream each SNDM allowed us to quantify using MALDI-MS the proportion of PCR products derived from the CNV region versus the external reference. In contrast to other approaches, setting up this genotyping method requires an affordable investment.

Vitamin-D pathway genes and HIV-1 disease progression in injection drug users.

Vitamin-D has pleiotropic effects on calcium and bone metabolism, cellular growth control, cell differentiation and modulation of both innate and acquired immune response. Previous studies revealed the association of vitamin-D receptor gene (VDR) polymorphism with infection diseases including HIV-1 infection. To assess for association between polymorphisms of vitamin-D pathway genes CYP27B1, vitamin-D binding protein (VDBP) and VDR with HIV-1 infection, disease progression to acquired immunodeficiency syndrome (AIDS) was analysed according to CDC93 criteria in a cohort of 185 HIV-1 seroprevalent patients belonging to the injection drug users. Genotype data was obtained from rs10877012, rs3782130 and rs4646536 markers at CYP27B1 locus; rs7041 and rs4588 at VDBP locus; and rs11568820, rs4516035, rs2228570, rs1544410 and rs17878969 at VDR locus. Distribution of genotypes between patients grouped by outcome was compared by contingency table analysis. Marker-marker interaction was assessed by a MDR analysis. Assuming an additive model for VDR markers, a Kaplan-Meier survival analysis was employed to evaluate association with disease progression. Among vitamin-D pathway genes, VDR locus reveals specific 5'UTR and 3'UTR diplotype combinations associated with both, slower and faster progression to AIDS. Marker-marker interaction analysis indicates a strong interaction between VDR markers and a redundant effect for CYP27B1 markers. According to our results, VDR locus association follows an additive model in which increased genetic risk score for the VDR is directly correlated with AIDS progression rates. Our data supports a role of vitamin-D pathway gene variability on HIV-1 disease progression.

Absence of substantial copy number differences in a pair of monozygotic twins discordant for features of autism spectrum disorder.

Autism spectrum disorder (ASD) is a highly heritable disease (~0.9) with a complex genetic etiology. It is initially characterized by altered cognitive ability which commonly includes impaired language and communication skills as well as fundamental deficits in social interaction. Despite the large amount of studies described so far, the high clinical diversity affecting the autism phenotype remains poorly explained. Recent studies suggest that rare genomic variations, in particular copy number variation (CNV), may account for a significant proportion of the genetic basis of ASD. The use of disease-discordant monozygotic twins represents a powerful strategy to identify de novo and inherited CNV in the disorder. Here we present the results of a comparative genome hybridization (CGH) analysis with a pair of monozygotic twins affected of ASD with significant differences in their clinical manifestations that specially affect speech language impairment and communication skills. Array CGH was performed in three different tissues: blood, saliva, and hair follicle, in an attempt to identify germinal and somatic CNV regions that may explain these differences. Our results argue against a role of large CNV rearrangements as a molecular etiology of the observed differences. This forwards future research to explore de novo point mutation and epigenomic alterations as potential explanations of the observed clinical differences.

Association of BST-2 gene variants with HIV disease progression underscores the role of BST-2 in HIV type 1 infection.

We tested bone marrow stromal cell antigen 2 (BST-2) gene variants rs3217318, a 19-base-pair insertion/deletion polymorphism in the promoter region, and rs10415893, a tag single-nucleotide polymorphism in the 3' untranslated region, for their association with human immunodeficiency virus type 1 (HIV-1) infection and disease progression. The study included 356 subjects exposed to HIV-1 (185 with and 171 without infection) and 188 controls. The first decrease in the CD4(+) T-cell count to <200 cells/µL was used as the primary outcome, whereas the primary outcome plus initiation of any antiretroviral treatment was used as a secondary composite outcome. Association with progression was found for both rs3217318 and rs10415893, following an overdominant model. Diplotype analysis revealed faster progression to both outcomes for subjects carrying the Δ19_G/i19_A diplotype. Luciferase assay showed that a promoter sequence containing the i19 allele had the lowest expression levels, suggesting that i19 allele carriers could have less BST-2 expression, reducing their capability to retain viral particles. These results point to the relevance of BST-2 as a host genetic factor modifying HIV-1 disease progression.

Distribution of functional polymorphic variants of inflammation-related genes RANTES and CCR5 in long-lived individuals.

Although persistent inflammation has been related to unsuccessful aging, a pro-inflammatory status is the common phenotype in older people. To assess for a genetic component in the inflammatory status of the oldest we studied the distribution of two polymorphic chemokine pathway genes, RANTES and CCR5, in elderly. RANTES -403G/A and RANTES Int1.1T/C polymorphisms and CCR5Δ32 polymorphism were genotyped in 104 elderly and 110 controls. RANTES -403A and RANTES Int1.1C alleles have been associated with pro-inflammatory and anti-inflammatory status, respectively. CCR5Δ32 abrogates functional receptor expression of the pro-inflammatory CCR5-mediated action. Prevalence of RANTES -403G allele, associated in other studies with high RANTES production, was reduced in elderly males, compared with controls. In addition, RANTES pro-inflammatory haplotype -403A-Int1.1T was overrepresented in elderly males, while RANTES anti-inflammatory haplotype -403G-Int1.1C was overrepresented in elderly females. Our results suggest a sex-specific RANTES inflammatory genetic determinant that could contribute to the known sex-related differences in aging.

Association of androgen receptor gene, CAG and GGN repeat length polymorphism and impulsive-disinhibited personality traits in inmates: the role of short-long haplotype.

OBJECTIVE: This study analyses the association between impulsive-disinhibited personality traits and the androgen receptor CAG and GGN repeat polymorphisms in both inmates and control samples. METHODS: We used two samples: 153 inmates (mean age= 33.31 years; standard deviation: 8.6; range: 20-63) and 108 controls (mean age= 26.71 years; standard deviation: 9.68; range: 17-53). A disinhibited personality construct was measured using the following personality scales: Sensation Seeking, Aggression-Hostility, Psychoticism, Sensitivity to Reward, Novelty Seeking and Impulsivity. A factor analysis of the six scales provided a normalized z index that was taken as a measure of impulsive-disinhibited personality. RESULTS: Our data show that inmates carrying CAG short and GGN long haplotype group (short-long haplotype) obtained higher scores on all personality scales. Differences were found for the Impulsive Sensation-Seeking scale (age-adjusted multivariate analysis, P<0.016) and z index (P<0.036). When comparing extreme groups in the impulsive-disinhibited personality index (taking the 75th percentile as a cut-off), carriers of the short-long haplotype were more prevalent in the extreme high group (30 vs. 10%: unadjusted odds ratio=3.8; 95% confidence interval=1.5-9.8; age-adjusted odds ratio=4.4; 95% confidence interval=1.6-12; P<0.004). CONCLUSION: Our findings suggest that the androgen receptor CAG and GGN polymorphisms might influence impulsive-disinhibited personality traits.

Immunophenotype of vitamin D receptor polymorphism associated to risk of HIV-1 infection and rate of disease progression.

Vitamin-D-receptor (VDR) mediates immunomodulatory effects of vitamin-D3 (VD3). The VDR-rs1544410_GG polymorphism has been associated with delayed progression rates to AIDS and resistance to HIV-1 infection. The aim of the present study was to investigate differences in VD3 mediated effects on rs1544410 genotyped dendritic cells (DCs) and macrophages (MDM), key cells involved in HIV-1 infection. Immature DCs exhibited lower b-actin-normalized VDR mRNA expression in rs1544410_GG compared to cells with a rs1544410_AA genotype. VD3 response on cell differentiation markers (CD14 inhibition and CD209 induction) was two-fold higher in rs1544410_AA (CD209, p=0.012; CD14, p=0.02). HIV-1-LTR reporter gene activity in MDM was boosted by VD3; however, the effect was up to 50% higher in rs1544410_AA. We conclude that the rs1544410_AA association with progression to AIDS and resistance to HIV-1 appears to be linked to an enhanced response to VD3.