The Role of External Genital Lesions in Human Immunodeficiency Virus Seroconversion Among Men Participating in a Multinational Study.

BACKGROUND: Studies in women have shown an increased risk of human immunodeficiency virus (HIV) acquisition with prior human papilloma virus (HPV) infection; however, few studies have been conducted among men. Our objective was to assess whether HPV-related external genital lesions (EGLs) increase risk of HIV seroconversion among men. METHODS: A total of 1379 HIV-negative men aged 18 to 70 years from the United States, Mexico, and Brazil were followed for up to 7 years and underwent clinical examination for EGLs and blood draws every 6 months. Human immunodeficiency virus seroconversion was assessed in archived serum. Cox proportional hazards and marginal structural models assessed the association between EGL status and time to HIV seroconversion. RESULTS: Twenty-nine participants HIV seroconverted during follow-up. Older age was associated with a lower hazard of HIV seroconversion. We found no significant difference in the risk of HIV seroconversion between men with and without EGLs (adjusted hazard ratio, 0.94; 95% confidence interval, 0.32-2.74). Stratified analyses focusing on men that have sex with men found no association between EGLs and HIV seroconversion risk (hazards ratio, 0.63; 95% confidence interval, 0.00-1.86). CONCLUSIONS: External genital lesions were not associated with higher risk for HIV seroconversion in this multinational population, although statistical power was limited as there were few HIV seroconversions. Results may differ in populations at higher risk for HIV.

A Multi-Omic Analysis for Low Bone Mineral Density in Postmenopausal Women Suggests a RELATIONSHIP between Diet, Metabolites, and Microbiota.

The effect of microbiota composition and its health on bone tissue is a novel field for research. However, their associations with bone mineral density (BMD) have not been established in postmenopausal women. The present study investigates the relation of diet, the microbiota composition, and the serum metabolic profile in postmenopausal women with normal-BMD or with low-BMD. Ninety-two Mexican postmenopausal women were classified into normal-BMD (n = 34) and low-BMD (n = 58). The V4 hypervariable region was sequenced using the Miseq platform. Serum vitamin D was determined by chemiluminescence immunoassay. Serum concentrations of acyl-carnitines and amino acids were determined by electrospray tandem mass spectrometry. Diet was assessed by a food frequency questionnaire. The low-BMD group had fewer observed species, higher abundance of γ-Proteobacteria, lower consumption of lycopene, and lower concentrations of leucine, valine, and tyrosine compared with the normal-BMD group. These amino acids correlated positively with the abundance of Bacteroides. Lycopene consumption positively correlated with Oscillospira and negatively correlated with Pantoea genus abundance. Finally, the intestinal microbiota of women with vitamin D deficiency was related to Erysipelotrichaceae and Veillonellaceae abundance compared to the vitamin D non-deficient group. Associations mediated by the gut microbiota between diet and circulating metabolites with low-BMD were identified.

Serum Proteomic Analysis Reveals Vitamin D-Binding Protein (VDBP) as a Potential Biomarker for Low Bone Mineral Density in Mexican Postmenopausal Women.

Osteoporosis is a skeletal disease mainly affecting women over 50 years old and it represents a serious public health problem because of the high socioeconomic burden. This disease is characterized by deterioration of bone microarchitecture, low bone mineral density (BMD), and increased risk of fragility fractures. This study aimed to identify serum useful proteins as biomarkers for the diagnosis and/or prognosis of osteoporosis and fracture risk. We collected 446 serum samples from postmenopausal women aged ≥45 years old. Based on the BMD measurement, we classified the participants into three groups: osteoporotic, osteopenic, and normal. In an initial discovery stage, we conducted a proteomic approach using two-dimensional differential gel electrophoresis (2D-DIGE). The peptides into the spots of interest were identified through matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF/TOF). Enzyme-linked immunosorbent assay (ELISA) was performed to validate the proteins of interest. We identified 27 spots of interest when comparing low BMD versus normal BMD postmenopausal women. Based on their relevance in bone metabolism, we analyzed three proteins: ceruloplasmin (CP), gelsolin (GSN), and vitamin D-binding protein (VDBP). Our results demonstrated that low serum VDBP levels correlate with low BMD (osteopenic and osteoporotic). Therefore, VDBP could be considered as a novel, potential, and non-invasive biomarker for the early detection of osteoporosis.

Influence of Genetic and Non-Genetic Risk Factors for Serum Uric Acid Levels and Hyperuricemia in Mexicans.

Risk of hyperuricemia is modified by genetic and environmental factors. Our aim was to identify factors associated with serum uric acid levels and hyperuricemia in Mexicans. A pilot Genome-wide association study GWAS was performed in a subgroup of participants (n = 411) from the Health Workers Cohort Study (HWCS). Single nucleotide polymorphisms (SNPs) associated with serum uric acid levels were validated in all the HWCS participants (n = 1939) and replicated in independent children (n = 1080) and adult (n = 1073) case-control studies. The meta-analysis of the whole HWCS and replication samples identified three SLC2A9 SNPs: rs1014290 (p = 2.3 × 10-64), rs3775948 (p = 8.2 × 10-64) and rs11722228 (p = 1.1 × 10-17); and an ABCG2 missense SNP, rs2231142 (p = 1.0 × 10-18). Among the non-genetic factors identified, the visceral adiposity index, smoking, the metabolic syndrome and its components (waist circumference, blood pressure, glucose and hyperlipidemia) were associated with increased serum uric acid levels and hyperuricemia (p < 0.05). Among the female HWCS participants, the odds ratio for hyperuricemia was 1.24 (95% CI, 1.01-1.53) per unit increase in soft drink consumption. As reported in other studies, our findings indicate that diet, adiposity and genetic variation contribute to the elevated prevalence of hyperuricemia in Mexico.

The association between body mass index and anal canal human papillomavirus prevalence and persistence: the HIM study.

Background: While receptive anal sex is an established risk factor for anal human papillomavirus (HPV) infection and squamous cell carcinoma of the anus (SCCA), people with anal HPV infection and SCCA commonly report no lifetime receptive anal sex suggesting other factors may also increase risk for anal HPV infection and persistence. Given potential associations between obesity and conditions that may cause perianal or anal canal lesions, we hypothesized that body mass index (BMI) was associated with HPV infection. Methods: Genotyping for 36 HPV types was conducted on anal canal specimens from men, ages 18-70, from Brazil, Mexico, and the USA. Eligibility included no history of genital warts or HIV. Evaluable specimens were collected from 328 men having sex with men (MSM) and 1348 men having sex with women (MSW) who reported no lifetime receptive anal sex. Prevalence of anal HPV infection and six-month persistence by BMI were estimated in addition to adjusted prevalence ratios for the association between BMI and HPV infection. Results: Among MSW, obese men had a higher prevalence of HPV-16 in the anal canal (3.1%), compared to normal weight men (1.3%) although 95% CI overlapped. Among MSM, prevalence of HPV decreased with increasing BMI. A similar pattern was observed for persistence. After adjustment for confounders, obese MSW had 2.4 times higher odds of HPV-16 compared to normal weight men. Conclusions: BMI may be positively associated with anal HPV (especially HPV-16) among MSW and negatively associated with anal HPV among MSM which supports continued universal HPV vaccination programs.

Incidence of external genital lesions related to human papillomavirus among Mexican men. A cohort study / Incidencia de lesiones genitales externas relacionadas con el virus del papiloma humano entre hombres mexicanos. Un estudio de cohorte

Abstract: Objective: To determine external genital lesion (EGL) incidence -condyloma and penile intraepithelial neoplasia (PeIN)- and genital HPV-genotype progression to these EGLs. Materials and methods: Participants (healthy males 18-74y from Cuernavaca, Mexico, recruited 2005-2009, n=954) underwent a questionnaire, anogenital examination, and sample collection every six months; including excision biopsy on suspicious EGL with histological confirmation. Linear array assay PCR characterized 37 high/low-risk HPV-DNA types. EGL incidence and cumulative incidence were calculated, the latter with Kaplan-Meier. Results: EGL incidence was 1.84 (95%CI=1.42-2.39) per 100-person-years (py); 2.9% (95%CI=1.9-4.2) 12-month cumulative EGL. Highest EGL incidence was found in men 18-30 years: 1.99 (95%CI=1.22-3.25) per 100py. Seven subjects had PeIN I-III (four with HPV16). HPV11 most commonly progresses to condyloma (6-month cumulative incidence=44.4%, 95%CI=14.3-137.8). Subjects with high-risk sexual behavior had higher EGL incidence. Conclusion: In Mexico, anogenital HPV infection in men is high and can cause condyloma. Estimation of EGL magnitude and associated healthcare costs is necessary to assess the need for male anti-HPV vaccination.

Resumen: Objetivo: Determinar incidencia de lesiones genitales externas (LGE) -condiloma y neoplasia intraepitelial del pene (NIP)- y progresión de genotipos de VPH a LGE. Material y métodos: Se aplicaron cuestionarios, examen anogenital y recolección de muestras cada seis meses a hombres sanos (18-74 años, de Cuernavaca, México, reclutados 2005-2009, n=954) con biopsia y confirmación histológica. Se caracterizaron 37 tipos de ADN-VPH; se calculó incidencia de LGE (cumulativa con Kaplan-Meier). Resultados: Incidencia de LGE=1.84 (IC95%=1.42-2.39) por 100-persona-años (pa); 2.9% (IC95%=1.9-4.2) LGE acumulativa a 12 meses. Mayor incidencia de LGE entre hombres 18-30 años; 1.99 (IC95%=1.22-3.25) por 100pa. Siete sujetos tuvieron NIP I-III. VPH-11 más comúnmente progresa a condiloma (incidencia acumulativa a seis meses=44.4%, IC95%=14.3-137.8). Los sujetos con comportamiento sexual de alto riesgo tuvieron mayor incidencia de LGE. Conclusiones: En México la infección anogenital con VPH es alta y puede causar condiloma. La estimación de magnitud de LGE y los costos sanitarios asociados se necesita para evaluar la necesidad de vacunación contra VPH en hombres.

Prevalence and incidence of anal human papillomavirus infection in Mexican men: Need for universal prevention policies / Prevalencia e incidencia de infección por virus de papiloma humano en canal anal en hombres mexicanos: Necesidad de políticas de prevención universal

Abstract: Objective: Describe the natural history of anal HPV among men. Materials and methods: Prospective study among men 18-70 years (n=665), from Cuernavaca, Mexico who completed questionnaires and provided specimens (HPV genotyped) at enrollment and 1+ follow-up visit. HPV prevalence and incidence were estimated. Prevalence ratios were calculated with Poisson regression using robust variance estimation. Person-time for incident HPV infection was estimated using number of events modeled as Poisson variable for total person-months. Results: Anal infection prevalence: any HPV type=15%, high-risk=8.4%, HPV16=1.4%, tetravalent vaccine types (4vHPV)=4.4%, nonavalent vaccine types (9vHPV)=6.3%. Factors associated with prevalence: 50+ lifetime female sex partners (adjusted prevalence ratio, a PR=3.25, 95% CI:1.12-9.47), 10+ lifetime male sex partners (aPR=3.06, 95%CI:1.4-6.68), and 1+ recent male anal sex partners (aPR=2.28, 95%CI:1.15-4.5). Anal incidence rate: high-risk HPV=7.8/1 000 person-months (95%CI:6.0-10.1), HPV16=1.8/1 000 person-months (95%CI:1.1-2.9),4vHPV=3.4/1 000 person-months (95%CI:2.3-4.9) and 9vHPV=5.5/1000 person-months (95%CI:4.1-7.5). Conclusions: Implementation of universal HPV vaccination programs, including men, is a public health priority.

Resumen: Objetivo: Generar evidencia que apoye la vacunación universal contra VPH. Material y métodos: Estudio prospectivo con hombres 18-70 años (n=665) de Cuernavaca, México con cuestionarios y genotipificación de VPH en muestras (2+mediciones). Se estimó prevalencia e incidencia; se calcularon tasas de prevalencia con regresión Poisson. Se estimó persona-tiempo para infecciones incidentes. Resultados: Prevalencia de infección anal: cualquier tipo de VPH=15%, alto-riesgo=8.4%, VPH16=1.4%, tipos en vacuna tetravalente=4.4% y tipos en vacuna nonavalente=6.3%. Factores asociados con infección prevalente: 50+ parejas sexuales femeninas en la vida (tasa de prevalencia ajustada, TPa=3.25, IC95%:1.12-9.47); 10+ parejas sexuales masculinas en la vida (TPa=3.06, IC95%:1.4-6.68) y 1+ parejas masculinas (sexo anal) recientes (TPa=2.28, IC95%:1.15-4.5). Tasas de incidencia para infección anal: VPH alto-riesgo=7.8/1000 persona-meses (IC95%:6.0-10.1), VPH 16=1.8/1000 persona-meses (95%IC:1.1-2.9), tipos en vacuna tetravalente=3.4/1000 persona-meses y tipos en vacuna nonavalente=5.5/1000 persona-meses. Conclusiones: Implementación de programas de vacunación universal (incluyendo hombres) contra VPH es una prioridad en salud pública.

Identification of miR-708-5p in peripheral blood monocytes: Potential marker for postmenopausal osteoporosis in Mexican-Mestizo population.

IMPACT STATEMENT: This is the first study in which hsa-miR-708-5p has been identified in peripheral blood monocytes (osteoclast precursors) and associated with postmenopausal osteoporosis through small RNA-Sequencing, in an Admixed Mexican Mestizo population. By conducting in silico and bioinformatic analyzes, we identified target genes and important signaling pathways involved in bone metabolism pointing hsa-miR-708-5p as a candidate marker for osteoporosis in Mexican population. These approaches provide a landscape of the post-transcriptional regulation, which can be useful for the management of postmenopausal osteoporosis along with the potential use of microRNAs as markers for its early detection.

Serum miRNAs miR-140-3p and miR-23b-3p as potential biomarkers for osteoporosis and osteoporotic fracture in postmenopausal Mexican-Mestizo women.

Osteoporosis is a metabolic bone disorder characterized by low bone mineral density and decreased bone strength, leading to an increased risk of fractures with a consequent increase in morbidity and mortality. The current methods to estimate the fracture risk are very limited. microRNAs (miRNAs) have been considered as good biomarkers for many pathological processes, including osteoporosis. Some circulating miRNAs are associated with regulation of bone formation and differentiation of bone cells. The aim of this study, was to analyze the expression of miRNAs in serum of patients with osteoporosis (n = 20) and healthy controls (n = 20). Expression of 754 miRNAs was analyzed through quantitative real time RT-PCR arrays. Seven miRNAs showed significant differences between groups. The microRNAs miR-23b-3p, miR-140-3p and miR-885-5p were selected based on fold change and p-values (40.5, p = 0.038, 20.7, p = 0.045, and 2.2, p = 0.002; respectively) for validation in independent serum samples from patients with osteopenia (n = 28), osteoporosis (n = 26) and osteoporotic hip fracture (n = 21). After validation, we confirm differences across the groups for miR-23b-3p and miR-140-3p. Our data pointed miR-140-3p and miR-23b-3p as potential biomarkers candidates for osteoporosis in postmenopausal women.

Association between Vitamin D Deficiency and Single Nucleotide Polymorphisms in the Vitamin D Receptor and GC Genes and Analysis of Their Distribution in Mexican Postmenopausal Women.

Genome-wide association studies in people with European ancestry suggest that polymorphisms in genes involved in vitamin D (VD) metabolism have an effect on serum concentrations of 25-hydroxyvitamin D. However, nothing is known about these polymorphisms in populations with Amerindian ancestry. Our aim was to evaluate the association between genetic variants on the vitamin D receptor (VDR) and the vitamin D binding protein (GC) genes, involved in the VD pathway, and VD deficiency in 689 unrelated Mexican postmenopausal women. We also described the frequencies of these variants in 355 postmenopausal women from different ethnic groups. Based on our preliminary results of 400 unrelated Mexican postmenopausal women, three single nucleotide polymorphisms (SNPs) were selected for genotyping. The SNPs rs4516035 in VDR and rs2282679 in GC were associated with VD deficiency. Additionally, women who carried three risk alleles had a 3.67 times higher risk of suffering VD deficiency, compared to women with no risk alleles (p = 0.002). The rs4516035-C allele frequency in the Amerindian population was enriched in the South East region of Mexico. In contrast, the highest frequency of the rs2298850-C allele, a proxy for the tag SNP rs2282679, was observed in the South region. Our results indicate that genetic variants in VDR and GC genes are associated with VD deficiency in Mexican postmenopausal women. Moreover, an association was observed for the variants rs3794060 and rs4944957 of the DHCR7/NADSYN1 gene with osteopenia/osteoporosis.

Genetic variants in COL13A1, ADIPOQ and SAMM50, in addition to the PNPLA3 gene, confer susceptibility to elevated transaminase levels in an admixed Mexican population.

Non-alcoholic fatty liver disease (NAFLD) is the accumulation of extra fat in liver cells not caused by alcohol. Elevated transaminase levels are common indicators of liver disease, including NAFLD. Previously, we demonstrated that PNPLA3 (rs738409), LYPLAL1 (rs12137855), PPP1R3B (rs4240624), and GCKR (rs780094) are associated with elevated transaminase levels in overweight/obese Mexican adults. We investigated the association between 288 SNPs identified in genome-wide association studies and risk of elevated transaminase levels in an admixed Mexican-Mestizo sample of 178 cases of NAFLD and 454 healthy controls. The rs2896019, rs12483959, and rs3810622 SNPs in PNPLA3 and rs1227756 in COL13A1 were associated with elevated alanine aminotransferase (ALT, ≥40IU/L). A polygenic risk score (PRS) based on six SNPs in the ADIPOQ, COL13A1, PNPLA3, and SAMM50 genes was also associated with elevated ALT. Individuals carrying 9-12 risk alleles had 65.8% and 48.5% higher ALT and aspartate aminotransferase (AST) levels, respectively, than those with 1-4 risk alleles. The PRS showed the greatest risk of elevated ALT levels, with a higher level of significance than the individual variants. Our findings suggest a significant association between variants in COL13A1, ADIPOQ, SAMM50, and PNPLA3, and risk of NAFLD/elevated transaminase levels in Mexican adults with an admixed ancestry. This is the first study to examine high-density single nucleotide screening for genetic variations in a Mexican-Mestizo population. The extent of the effect of these variations on the development and progression of NAFLD in Latino populations requires further analysis.

Incidence of external genital lesions related to human papillomavirus among Mexican men. A cohort study.

OBJECTIVE: To determine external genital lesion (EGL) incidence -condyloma and penile intraepithelial neoplasia (PeIN)- and genital HPV-genotype progression to these EGLs. MATERIALS AND METHODS: Participants (healthy males 18- 74y from Cuernavaca, Mexico, recruited 2005-2009, n=954) underwent a questionnaire, anogenital examination, and sample collection every six months;including excision biopsy on suspicious EGL with histological confirmation.Linear array assay PCR characterized 37 high/low-risk HPV-DNA types. EGL incidence and cumulative incidence were calculated, the latter with Kaplan-Meier. RESULTS: EGL incidence was 1.84 (95%CI=1.42-2.39) per 100-person-years (py); 2.9% (95%CI=1.9-4.2) 12-month cumulative EGL.Highest EGL inci- dence was found in men 18-30 years:1.99 (95%CI=1.22-3.25) per 100py. Seven subjects had PeIN I-III (four with HPV16). HPV11 most commonly progresses to condyloma (6-month cumulative incidence=44.4%, 95%CI=14.3-137.8). Subject with high-risk sexual behavior had higher EGL incidence. CONCLUSIONS: In Mexico, anogenital HPV infection in men is high and can cause condyloma. Estimation of EGL magnitude and associated healthcare costs is necessary to assess the need for male anti-HPV vaccination.

OBJETIVO: Determinar incidencia de lesiones genitales externas (LGE) ­condiloma y neoplasia intraepitelial del pene (NIP)­ y progresión de genotipos deVPH a LGE. MATERIAL Y MÉTODOS: Se aplicaron cuestionarios,examen anogenital y recolección de muestras cada seis meses a hombres sanos (18-74 años, de Cuernavaca, México, reclutados 2005-2009, n=954) con biopsia y confirmación histológica. Se caracteri- zaron 37 tipos de ADN-VPH; se calculó incidencia de LGE (cumulativa con Kaplan-Meier). RESULTADOS: Incidencia de LGE=1.84 (IC95%=1.42-2.39) por 100-persona-años (pa); 2.9% (IC95%=1.9-4.2) LGE acumulativa a 12 meses. Mayor incidencia de LGE entre hombres 18-30 años; 1.99 (IC95%=1.22-3.25) por 100pa.Siete sujetos tuvieron NIP I-III. VPH-11 más comúnmente progresa a condiloma (incidencia acumulativa a seis meses=44.4%, IC95%=14.3-137.8). Los sujetos con comportamiento sexual de alto riesgo tuvieron mayor incidencia de LGE. CONCLUSIONES: En México la infección anogenital conVPH es alta y puede causar condiloma. La estimación de magnitud de LGE y los costos sanitarios asociados se necesita para evaluar la necesidad de vacunación contra VPH en hombres.

Prevalence and incidence of anal human papillomavirus infection in Mexican men: Need for universal prevention policies.

OBJECTIVE: Describe the natural history of anal HPV among men. MATERIALS AND METHODS: Prospective study among men 18-70 years (n=665), from Cuernavaca, Mexico who completed questionnaires and provided specimens (HPV genotyped) at enrollment and 1+ follow-up visit. HPV prevalence and incidence were estimated. Prevalence ratios were calculated with Poisson regression using robust variance estimation. Person-time for incident HPV infection was estimated using number of events modeled as Poisson variable for total person-months. RESULTS: Anal infection prevalence: any HPV type=15%, high-risk=8.4%, HPV16=1.4%, tetravalent vaccine types (4vHPV)=4.4%, nonavalent vaccine types (9vHPV)=6.3%. Factors associated with prevalence: 50+ lifetime female sex partners (adjusted prevalence ratio, a PR=3.25, 95% CI:1.12- 9.47), 10+ lifetime male sex partners (aPR=3.06, 95%CI:1.4- 6.68), and 1+ recent male anal sex partners (aPR=2.28, 95%CI:1.15-4.5). Anal incidence rate: high-risk HPV=7.8/1000 person-months (95%CI:6.0-10.1), HPV16=1.8/1000 personmonths (95%CI:1.1-2.9),4vHPV=3.4/1000 person-months (95%CI:2.3-4.9) and 9vHPV=5.5/1000 person-months (95%CI:4.1-7.5). CONCLUSIONS: Implementation of universal HPV vaccination programs, including men, is a public health priority.

OBJETIVO: Generar evidencia que apoye la vacunación universal contra VPH. MATERIAL Y MÉTODOS: Estudio prospectivo con hombres 18-70 años (n=665) de Cuernavaca, México con cuestionarios y genotipificación de VPH en muestras (2+mediciones). Se estimó prevalencia e incidencia; se calcularon tasas de prevalencia con regresión Poisson. Se estimó persona-tiempo para infecciones incidentes. RESULTADOS: Prevalencia de infección anal: cualquier tipo de VPH=15%, altoriesgo=8.4%, VPH16=1.4%, tipos en vacuna tetravalente=4.4% y tipos en vacuna nonavalente=6.3%. Factores asociados con infección prevalente: 50+ parejas sexuales femeninas en la vida (tasa de prevalencia ajustada, TPa=3.25, IC95%:1.12-9.47); 10+ parejas sexuales masculinas en la vida (TPa=3.06, IC95%:1.4- 6.68) y 1+ parejas masculinas (sexo anal) recientes (TPa=2.28, IC95%:1.15-4.5). Tasas de incidencia para infección anal: VPH alto-riesgo=7.8/1000 persona-meses (IC95%:6.0-10.1), VPH 16=1.8/1000 persona-meses (95%IC:1.1-2.9), tipos en vacuna tetravalente=3.4/1000 persona-meses y tipos en vacuna nonavalente=5.5/1000 persona-meses. CONCLUSIONES: mplementación de programas de vacunación universal (incluyendo hombres) contra VPH es una prioridad en salud pública.

Identification of microRNAs in human circulating monocytes of postmenopausal osteoporotic Mexican-Mestizo women: A pilot study.

MicroRNAs (miRNAs or miRs) are a class of short non-coding RNAs that serve an important regulatory role in living organisms. These molecules are associated with multiple biological processes and are potential biomarkers in multiple diseases. The present study aimed to further identify miRNAs that are differentially expressed in circulating monocytes (CMCs) from postmenopausal Mexican-Mestizo women. Microarray analyses of monocytes using Affymetrix miRNA 4.0 and Human Genome U133 Plus 2.0 arrays were performed in 6 normal and 6 osteoporotic women, followed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) validation. The overexpression of miR-1270, miR-548×-3p and miR-8084 were detected in the osteoporosis compared with the normal group according to the microarray analysis; miR-1270, a miRNA with several target genes associated with bone remodeling, was validated by RT-qPCR. Bioinformatics analysis identified that interferon regulatory factor 8 (IRF8) is the most likely target gene of miR-1270, which is associated with osteoclastogenesis. Furthermore, the findings of the present study demonstrate that an upregulation of miR-1270 may reduce the gene expression of IRF8 in CMCs (osteoclast precursors), implicating its potential role in leading to low bone mineral density and contributing to osteoporosis development in postmenopausal women.

A Pilot Genome-Wide Association Study in Postmenopausal Mexican-Mestizo Women Implicates the RMND1/CCDC170 Locus Is Associated with Bone Mineral Density.

To identify genetic variants influencing bone mineral density (BMD) in the Mexican-Mestizo population, we performed a GWAS for femoral neck (FN) and lumbar spine (LS) in Mexican-Mestizo postmenopausal women. In the discovery sample, 300,000 SNPs were genotyped in a cohort of 411 postmenopausal women and seven SNPs were analyzed in the replication cohort (n = 420). The combined results of a meta-analysis from the discovery and replication samples identified two loci, RMND1 (rs6904364, P = 2.77 × 10-4) and CCDC170 (rs17081341, P = 1.62 × 10-5), associated with FN BMD. We also compared our results with those of the Genetic Factors for Osteoporosis (GEFOS) Consortium meta-analysis. The comparison revealed two loci previously reported in the GEFOS meta-analysis: SOX6 (rs7128738) and PKDCC (rs11887431) associated with FN and LS BMD, respectively, in our study population. Interestingly, rs17081341 rare in Caucasians (minor allele frequency < 0.03) was found in high frequency in our population, which suggests that this association could be specific to non-Caucasian populations. In conclusion, the first pilot Mexican GWA study of BMD confirmed previously identified loci and also demonstrated the importance of studying variability in diverse populations and/or specific populations.

Interaction between FTO rs9939609 and the Native American-origin ABCA1 rs9282541 affects BMI in the admixed Mexican population.

BACKGROUND: The aim of this study was to explore whether interactions between FTO rs9939609 and ABCA1 rs9282541 affect BMI and waist circumference (WC), and could explain previously reported population differences in FTO-obesity and FTO-BMI associations in the Mexican and European populations. METHODS: A total of 3938 adults and 636 school-aged children from Central Mexico were genotyped for both polymorphisms. Subcutaneous and visceral adipose tissue biopsies from 22 class III obesity patients were analyzed for FTO and ABCA1 mRNA expression. Generalized linear models were used to test for associations and gene-gene interactions affecting BMI, WC and FTO expression. RESULTS: FTO and ABCA1 risk alleles were not individually associated with higher BMI or WC. However, in the absence of the ABCA1 risk allele, the FTO risk variant was significantly associated with higher BMI (P = 0.043) and marginally associated with higher WC (P = 0.067), as reported in Europeans. The gene-gene interaction affecting BMI and WC was statistically significant only in adults. FTO mRNA expression in subcutaneous abdominal adipose tissue according to ABCA1 genotype was consistent with these findings. CONCLUSIONS: This is the first report showing evidence of FTO and ABCA1 gene variant interactions affecting BMI, which may explain previously reported population differences. Further studies are needed to confirm this interaction.

Comparison of the Natural History of Genital HPV Infection among Men by Country: Brazil, Mexico, and the United States.

Background: Male genital human papillomavirus (HPV) prevalence and incidence has been reported to vary by geographical location. Our objective was to assess the natural history of genital HPV by country among men with a median of 48 months of follow-up.Methods: Men ages 18-70 years were recruited from United States (n = 1,326), Mexico (n = 1,349), and Brazil (n = 1,410). Genital specimens were collected every 6 months and HPV genotyping identified 37 HPV genotypes. Prevalence of HPV was compared between the three countries using the Fisher exact test. Incidence rates and 95% confidence intervals were calculated. The median time to HPV clearance among men with an incident infection was estimated using the Kaplan-Meier method.Results: The prevalence and incidence of the genital HPV types known to cause disease in males (HPV 16 and 6) was significantly higher among men from Brazil than men from Mexico. Prevalence and incidence of those genital HPV types in the United States varied between being comparable with those of Mexico or Brazil. Although genital HPV16 duration was significantly longer in Brazil (P = 0.04) compared with Mexico and the United States, HPV6 duration was shortest in Brazil (P = 0.03) compared with Mexico and the United States.Conclusions: Men in Brazil and Mexico often have similar, if not higher prevalence of HPV compared with men from the United States.Impact: Currently, there is no routine screening for genital HPV among males and while HPV is common in men, and most naturally clear the infection, a proportion of men do develop HPV-related diseases. Men may benefit from gender-neutral vaccine policies. Cancer Epidemiol Biomarkers Prev; 26(7); 1043-52. ©2017 AACR.

Comparison of anal HPV natural history among men by country of residence: Brazil, Mexico, and the United States.

OBJECTIVES: Globally, anal cancer incidence is rare, but is increasing in some world regions. Our objective was to assess differences in anal HPV natural history in three countries. METHODS: Men aged 18-70 years were recruited from the US (n = 634), Mexico (n = 665), and Brazil (n = 731). Anal specimens were collected every six-months. HPV genotyping was assessed by Linear Array. Anal HPV prevalence was compared using the Fisher's exact test. HPV infection incidence rates (IR) and 95% confidence intervals (CI) were calculated. RESULTS: Any anal HPV prevalence was highest among men from Brazil (24%) compared to Mexico (15%) and the US (15%). When stratified by sexual history, the prevalence of any HPV among MSM/MSMW was 43%, 37%, and 45% and 9%, 12%, and 10% for MSW from Brazil, Mexico, and US, respectively. Any HPV incidence was significantly higher among men from Brazil compared to US men (IRR = 2.4, 95% CI = 1.7-3.4) and comparable between men from Mexico and the US (IRR = 1.2, 95% CI = 0.8-1.8). CONCLUSION: Men in Brazil and Mexico often have similar, if not higher incidence of anal HPV compared to men from the U.S., and may benefit from gender neutral HPV vaccine policies.

Country-specific HPV-related genital disease among men residing in Brazil, Mexico and The United States: The HIM study.

The purpose of this study was to assess whether the incidence of histopathologically confirmed condyloma and penile intraepithelial neoplasia (PeIN) and rates of genital HPV infection progression to these lesions differs by country (Brazil, Mexico and the U.S.). At each visit, lesions were biopsied and were categorized by pathologic diagnoses. The Linear Array genotyping method was used to identify HPV genotypes from genital swabs, while the INNO-LiPA HPV Genotyping Extra method was used for tissue specimens. Age-specific analyses were conducted for lesion incidence by country, with Kaplan-Meier estimation of cumulative incidence. The proportion of HPV infections that progressed to condyloma and PeIN, the median time to lesion development and the incidence rates were estimated by country. When comparing demographic and sexual characteristics across the three countries, sexual orientation (p = 0.008) and lifetime number of female sexual partners (p < 0.0001) were differentially associated with lesion incidence in the three countries. Condyloma incidence in Brazil and the U.S. decreased with age, while incidence remained constant across the lifespan in Mexico. There were no differences by country and age for PeIN incidence. HPV types 6 and 11 were the most common types to progress to condyloma and HPV types 16, 6 and 11 were the most common types to progress to PeIN in all three countries. The continuous risk of condyloma and PeIN across all age groups and countries in this study emphasizes the need to ensure that strong HPV immunity, such as that obtained through vaccination, is maintained across the lifespan of men.

Association between PNPLA3 (rs738409), LYPLAL1 (rs12137855), PPP1R3B (rs4240624), GCKR (rs780094), and elevated transaminase levels in overweight/obese Mexican adults.

There is scarce information about the link between specific single-nucleotide polymorphisms (SNPs) and risk of liver disease among Latinos, despite the disproportionate burden of disease among this population. Our aim was to investigate nine SNPs in or near the following genes: PNPLA3, LYPLAL1, PPP1R3B, GCKR, NCAN, IRS1, PPARG, and ADIPOR2 and examine their association with persistently elevated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels in Mexican adults. Data and samples were collected from 741 participants in the Mexican Health Worker Cohort Study, in Cuernavaca, Mexico. We identified 207 cases who had persistently elevated levels of ALT or AST (≥40 U/L) and 534 controls with at least two consecutive normal ALT or AST results in a 6 month period, during 2004-2006 and 2011-2013. TaqMan assays were used to genotype the SNPs. The risk allele of PNPLA3 rs738409 was found to be associated with persistently elevated levels of ALT or AST, adjusting for age, sex, BMI, type 2 diabetes, and ancestry: (OR 2.28, 95 % CI 1.13, 4.58). A significant association was found between the LYPLAL1, PPP1R3B, and GCKR risk alleles and elevated ALT or AST levels among overweight/obese adults. These results suggest that among Mexicans, the PNPLA3 (rs738409), LYPLAL1 (rs12137855), PPP1R3B (rs4240624), and GCKR (rs780094) polymorphisms may be associated with a greater risk of chronic liver disease among overweight adults. This study is the first to examine these nine SNPs in a sample of adults in Mexico.