Association Study between Antioxidant Nutrient Intake and Low Bone Mineral Density with Oxidative Stress-Single Nucleotide Variants: GPX1 (rs1050450 and rs17650792), SOD2 (rs4880) and CAT (rs769217) in Mexican Women.

Oxidative stress is essential in developing multiple bone metabolism diseases, including osteoporosis. Single-nucleotide variants (SNVs) have been associated with oxidative stress, promoting an imbalance between the production of reactive oxygen species and the ability to neutralize them, and it has been reported that antioxidant nutrient intake can influence bone mineral density (BMD). This work reports the association between oxidative stress-related SNVs (GPX1-rs1050450, rs17650792, SOD2-rs4880, and CAT-rs769217), BMD, and antioxidant nutrient intake. The study included 1269 Mexican women from the Health Workers Cohort Study. Genotyping was performed using predesigned TaqMan assays. Dietary data were collected using a 116-item semi-quantitative food frequency questionnaire. A dietary antioxidant quality score (DAQS) was used to estimate antioxidant-nutrient intake. Association analysis was estimated via linear, logistic, or quantile regression models. The results showed an association of the rs1050450-A and rs17650792-A alleles with femoral neck BMD (p = 0.038 and p = 0.017, respectively) and the SNV rs4880-A allele with total hip BMD (p = 0.026) in respondents aged 45 years or older. In addition, antioxidant-nutrient intake was associated with the rs4880-GG genotype, being significant for fiber (p = 0.007), riboflavin (p = 0.005), vitamin B6 (p = 0.034), and vitamin D (p = 0.002). The study showed an association between oxidative stress-related SNVs, BMD, and antioxidant-nutrient intake in Mexican women. Therefore, treatments for low BMD could be developed based on antioxidant supplementation.

Association of MARC1, ADCY5, and BCO1 Variants with the Lipid Profile, Suggests an Additive Effect for Hypertriglyceridemia in Mexican Adult Men.

Epidemiological studies have reported that the Mexican population is highly susceptible to dyslipidemia. The MARC1, ADCY5, and BCO1 genes have recently been involved in lipidic abnormalities. This study aimed to analyze the association of single nucleotide polymorphisms (SNPs) rs2642438, rs56371916, and rs6564851 on MARC1, ADCY5, and BCO1 genes, respectively, with the lipid profile in a cohort of Mexican adults. We included 1900 Mexican adults from the Health Workers Cohort Study. Demographic and clinical data were collected through a structured questionnaire and standardized procedures. Genotyping was performed using a predesigned TaqMan assay. A genetic risk score (GRS) was created on the basis of the three genetic variants. Associations analysis was estimated using linear and logistic regression. Our results showed that rs2642438-A and rs6564851-A alleles had a risk association for hypertriglyceridemia (OR = 1.57, p = 0.013; and OR = 1.33, p = 0.031, respectively), and rs56371916-C allele a trend for low HDL-c (OR = 1.27, p = 0.060) only in men. The GRS revealed a significant association for hypertriglyceridemia (OR = 2.23, p = 0.022). These findings provide evidence of an aggregate effect of the MARC1, ADCY5, and BCO1 variants on the risk of hypertriglyceridemia in Mexican men. This knowledge could represent a tool for identifying at-risk males who might benefit from early interventions and avoid secondary metabolic traits.

Single-nucleotide polymorphism rs10036727 in the SLIT3 gene is associated with osteoporosis at the femoral neck in older Mexican postmenopausal women.

AIMS: Osteoporosis (OP) remains a major public health problem worldwide. The most serious complications of this disease are fragility fractures, which increase morbidity and mortality. Management of OP represents an economic burden for health systems. Therefore, it is necessary to develop new screening strategies to identify the population at risk and implement preventive measures. We previously identified the SNPs rs3801387 in WNT16, rs7108738 in SOX6, rs10036727 in SLIT3 and rs7584262 in PKDCC as associated with bone mineral density in postmenopausal women through a genome-wide association study. The aim of this study was to validate those SNPs in two independent cohorts of non-related postmenopausal women. MATERIALS AND METHODS: We included 1160 women classifying them as normal, osteopenic or osteoporotic and a group with hip fragility fracture. Genotyping was performed using predesigned TaqMan assays. RESULTS: The variants rs10036727 and rs7108738 showed a significant association with BMD at the femoral neck. SLIT3 has been previously proposed as a potential biomarker and therapeutic resource. CONCLUSIONS: Our results provide new evidence regarding a possible involvement of SLIT3 in bone metabolisms and encourage the development of more studies in different populations to support these observations.

Trastorno por atracón, depresión, ansiedad y gen del neuropéptido relacionado con Agouti en pacientes con cirugía bariátrica / Binge eating disorder, depression, anxiety and Agouti gen related neuropeptide in patients with bariatric surgery

Resumen El objetivo de este estudio retroprospectivo fue analizar la relación de la sintomatología de depresión, de ansiedad y el trastorno por atracón (TPA) con el gen del neuropéptido relacionado con Agouti en pacientes sometidos a cirugía bariátrica. Participó una cohorte de 249 adultos (edad media = 41.1, DE =11.3), 64.1% mujeres y 35.9% hombres. La evaluación de la sintomatología depresiva, de ansiedad y de TPA se llevó a cabo a través de una entrevista semiestructurada. Además, se calculó el índice de masa corporal y se tomaron muestras de sangre para realizar un análisis de discriminación alélica. Del total de pacientes, un 20.2% fueron diagnosticados con TPA, encontrando una asociación de este trastorno con una menor pérdida de peso posterior a la cirugía bariátrica a los 6,12, 18 y 24 meses. Las medidas de depresión y de ansiedad no difirieron entre pacientes con TPA vs. sin TPA. Los pacientes con un alelo mutante en el gen del neuropéptido relacionado con Agouti tuvieron un riesgo 2.6 veces mayor de presentar TPA (IC 95% 1.0-6.8; p = 0.04). Además, el TPA parece ser más frecuente en pacientes con el gen del neuropéptido relacionado con Agouti mutado. Destaca la necesidad de que en el estudio de la obesidad se aborden tanto los aspectos psicológicos como los genéticos.

Abstract The objective of this retrospective study was to analyze the relationship between the symptoms of depression, anxiety and binge eating disorder (BED) with the gene related to the Agouti neuropeptide in patients undergoing bariatric surgery. A cohort of 249 adults (average age = 41.1, SD = 11.3), 64.1% women and 35.9% men, were included. The assessment of depression, anxiety and BED symptoms was carried out through a semi-structured interview. In addition, the body mass index was calculated, and blood samples were taken for an allelic discrimination analysis. Of the total number of patients 20.2% were diagnosed with BED, finding an association of this disorder with a lower weight loss after bariatric surgery at 6, 12, 18 and 24 months. The measures of depression and anxiety did not differ between patients with BED vs. without BED. Patients with a mutant allele in the gene related to the Agouti neuropeptide were 2.6 times more likely to present BED (95% C11.0-6.8, P = 0.04). In addition, BED appears to be more frequent in patients with a gene related to the Agouti neuropeptide mutated. When obesity is studied, it is emphasized the need to address both psychological and genetic factors.

Homozygosity for the WRN Helicase-Inactivating Variant, R834C, does not confer a Werner syndrome clinical phenotype.

Loss-of-function mutations in the WRN helicase gene cause Werner syndrome- a progeroid syndrome with an elevated risk of cancer and other age-associated diseases. Large numbers of single nucleotide polymorphisms have been identified in WRN. We report here the organismal, cellular, and molecular phenotypes of variant rs3087425 (c. 2500C > T) that results in an arginine to cysteine substitution at residue 834 (R834C) and up to 90% reduction of WRN helicase activity. This variant is present at a high (5%) frequency in Mexico, where we identified 153 heterozygous and three homozygous individuals among 3,130 genotyped subjects. Family studies of probands identified ten additional TT homozygotes. Biochemical analysis of WRN protein purified from TT lymphoblast cell lines confirmed that the R834C substitution strongly and selectively reduces WRN helicase, but not exonuclease activity. Replication track analyses showed reduced replication fork progression in some homozygous cells following DNA replication stress. Among the thirteen TT homozygotes, we identified a previously unreported and statistically significant gender bias in favor of males (p = 0.0016), but none of the clinical findings associated with Werner syndrome. Our results indicate that WRN helicase activity alone is not rate-limiting for the development of clinical WS.

Analysis of Gene Candidate SNP and Ancestral Origin Associated to Obesity and Postoperative Weight Loss in a Cohort of Obese Patients Undergoing RYGB.

INTRODUCTION: Obesity is the result of a complex interaction between multiple genetic traits and psychological, behavioral, nutritional and environmental factors. OBJECTIVES: The aims of the study were (a) to comparatively evaluate the presence of 20 candidate gene single nucleotide polymorphisms (SNPs) in morbidly obese patients, (2) their association to comorbid conditions and (3) their impact on weight loss after a Roux-en-Y gastric bypass (RYGB). PATIENTS AND METHODS: Two hundred forty-nine patients were eligible for this study. Clinical, anthropometric, biochemical and demographic variables were analyzed. Body mass index (BMI) and composition were assessed by bioelectrical impedance. Twenty SNPs were included for analysis. RESULTS: There were 168 Mexican mestizos (67.5 %) and 81 (32.5 %) patients with other ancestral origin. One hundred fifty-nine (64.1 %) were females. Mean ± SD age of the general cohort was 41.1 ± 11.3 years (17-71). Preoperative mean ± SD BMI was 42.5 ± 6.5 kg/m2. There were no significant differences between mestizo and non-mestizo for most SNPs except for IFI, LIPC, and ST8SIA2. FTO (OR = 1.71; CI95 % = 1.14-2.57; p = 0.008) and APOB (OR = 0.31; CI95 % = 0.14-0.72; p = 0.004) result is statistically associated to high blood pressure and FTO (OR = 2.0; CI95 % = 1.3-3.1; p = 0.001), GNB3 (OR = 2.69; CI95 % = 1.0-7.2; p = 0.04), IFI30 (OR = 2.0; CI95 % = 1.16-3.6; p = 0.01), and MC4R (OR = 1.81; CI95 % = 1.13-2.9; p = 0.01) to type 2 diabetes (T2D). Based on ANOVA analysis, POMC (rs1042571) was the SNP most significantly associated to a higher weight loss after RYGB. CONCLUSIONS: Obese patients have similar SNP frequencies. Several SNP results are statistically associated to high blood pressure and T2D. POMC was significantly associated to a higher surgically induced weight loss.