AIM: To identify gene mutations in PRSS1 and SPINK1 in individuals with early onset idiopathic chronic or recurrent acute pancreatitis.METHODS: The cationic trypsinogen gene(PRSS1; exons 2 and 3) and ...the serine protease inhibitor Kazal 1 gene(SPINK1; exon 3) were selectively amplified and sequenced from blood samples of 19 patients admitted to the Pancreas Clinic at our institution with chronic pancreatitis and/or idiopathic recurrent acute pancreatitis that were diagnosed or with onset before age 35. Fifty healthy volunteers served as controls. Whole blood samples were collected and gene specific sequences were amplified by polymerase chain reaction(PCR). All PCR products were subsequently sequenced in order to identify the presence of any mutations.RESULTS: Nineteen patients with pancreatitis(14 males; median age 24 years, range 15-48 years) were included in this study, of which five showed the presence of gene mutations. Direct sequencing results indicated the presence of two previously unidentified mutations in exon 2 of PRSS1(V39E and N42S) in two patients with recurrent acute pancreatitis. Two cases had the N34 S SPINK1 mutation. Analysis of the relatives of one patient homozygous for this mutation showed that five of the six family members carried the N34 S SPINK1 mutation. Of these members, three were healthy heterozygous carriers and two were homozygotes(one sibling had diabetes, the other was healthy). Another patient was heterozygous for a novel SPINK1 mutation located on exon 3(V46D). All members from this patient’s family had normal genotypes, indicating that it was a de novo mutation. No mutations in either gene were present in the control subjects. CONCLUSION: Two novel PRSS1 mutations and one novel SPINK1 mutation were identified in Mexican patients with early onset idiopathic recurrent acute pancreatitis.
Metabolic syndrome (MetS) is a group of several metabolic conditions predisposing to chronic diseases. Individuals diagnosed with MetS are physiologically heterogeneous, with significant sex-specific ...differences. Therefore, we aimed to investigate the potential sex-specific serum modifications of amino acids and acylcarnitines (ACs) and their relationship with MetS in the Mexican population. This study included 602 participants from the Health Workers Cohort Study. Forty serum metabolites were analyzed using a targeted metabolomics approach. Multivariate regression models were used to test associations of clinical and biochemical parameters with metabolomic profiles. Our findings showed a serum amino acid signature (citrulline and glycine) and medium-chain ACs (AC14:1, AC10, and AC18:10H) associated with MetS. Glycine and AC10 were specific metabolites representative of discrimination according to sex-dependent MetS. In addition, we found that glycine and short-chain ACs (AC2, AC3, and AC8:1) are associated with age-dependent MetS. We also reported a significant correlation between body fat and metabolites associated with sex-age-dependent MetS. In conclusion, the metabolic profile varies by MetS status, and these differences are sex-age-dependent in the Mexican population.
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 (
= 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 (
= 1939) and replicated in independent children (
= 1080) and adult (
= 1073) case-control studies. The meta-analysis of the whole HWCS and replication samples identified three
SNPs:
(
= 2.3 × 10
),
(
= 8.2 × 10
) and
(
= 1.1 × 10
); and an
missense SNP,
(
= 1.0 × 10
). 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 (
< 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.
Genome-wide association studies (GWAS) have identified copy number variants (CNVs) associated with obesity in chromosomal regions 1p31.1, 10q11.22, 11q11, 16p12.3, and recently 1p21.1, which contains ...the salivary amylase gene (
). Recent evidence suggests this enzyme may influence gut microbiota composition through carbohydrate (mainly starch) degradation. The role of these CNVs in obesity has been scarcely explored in the Latino population, and thus the aim of our study was to evaluate the association of 1p31.1, 10q11.22, 11q11, 16p12.3 and 1p21.1 CNVs with obesity in 921 Mexican children, to replicate significant associations in 920 Mexican adults, and to analyze the association of
copy number with gut microbiota in 75 children and 45 adults. Of the five CNVs analyzed, 1q11 CNV was significantly associated with obesity in children, but not in adults. Only
CNV was significantly associated with obesity in both age groups. Moreover, gut microbiota analyses revealed a positive correlation between
copy number and
abundance. This genus has enzymes and gene clusters essential for complex polysaccharide degradation and utilization. To our knowledge, this is the first study to analyze the association of these five CNVs in the Mexican population and to report a correlation between
CN and gut microbiota in humans.
Hair plays an important role in primates and is clearly subject to adaptive selection. While humans have lost most facial hair, eyebrows are a notable exception. Eyebrow thickness is heritable and ...widely believed to be subject to sexual selection. Nevertheless, few genomic studies have explored its genetic basis. Here, we performed a genome-wide scan for eyebrow thickness in 2961 Han Chinese. We identified two new loci of genome-wide significance, at 3q26.33 near SOX2 (rs1345417: P = 6.51×10(-10)) and at 5q13.2 near FOXD1 (rs12651896: P = 1.73×10(-8)). We further replicated our findings in the Uyghurs, a population from China characterized by East Asian-European admixture (N = 721), the CANDELA cohort from five Latin American countries (N = 2301), and the Rotterdam Study cohort of Dutch Europeans (N = 4411). A meta-analysis combining the full GWAS results from the three cohorts of full or partial Asian descent (Han Chinese, Uyghur and Latin Americans, N = 5983) highlighted a third signal of genome-wide significance at 2q12.3 (rs1866188: P = 5.81×10(-11)) near EDAR. We performed fine-mapping and prioritized four variants for further experimental verification. CRISPR/Cas9-mediated gene editing provided evidence that rs1345417 and rs12651896 affect the transcriptional activity of the nearby SOX2 and FOXD1 genes, which are both involved in hair development. Finally, suitable statistical analyses revealed that none of the associated variants showed clear signals of selection in any of the populations tested. Contrary to popular speculation, we found no evidence that eyebrow thickness is subject to strong selective pressure.
ABCA1 genetic variation is known to play a role in HDL-C levels and various studies have also implicated ABCA1 variation in cardiovascular risk. The functional ABCA1/R230C variant is frequent in the ...Mexican population and has been consistently associated with low HDL-C concentrations. Although it has been associated with other cardiovascular risk factors such as obesity and type 2 diabetes mellitus, it is not known whether it is associated with coronary artery disease (CAD).
The purpose of the study was to analyze whether the ABCA1/R230C variant is associated with premature CAD in a case-control association study (GEA or Genetics of Atherosclerotic Disease), and to explore whether BMI modulates the effect of the C230 allele on other metabolic traits using a population-based design.
The C230 allele was significantly associated with both lower HDL-C levels and a lower risk of premature CAD as compared to controls (OR = 0.566; P(add) = 1.499×10(-5)). In addition, BMI modulated the effect of R230C on body fat distribution, as the correlation between BMI and visceral to subcutaneous adipose tissue (a metric of the propensity to store fat viscerally as compared to subcutaneously) was negative in RR homozygous individuals, but positive in premenopausal women bearing the C230 allele, with a statistically significant interaction (P = 0.005). BMI-R230C interaction was also significant for triglyceride levels in women regardless of their menopausal status (P = 0.036).
This is the first study assessing the effect of the R230C/ABCA1 variant in remature CAD. C230 was associated with both decreased HDL-C levels and a lower risk of premature CAD, and gender-specific BMI-R230C interactions were observed for different metabolic traits. These interactions may help explain inconsistencies in associations, and underscore the need to further analyze interactions of this functional and frequent variant with diet, exercise and other environmental factors.
Dietary fiber (DF) is a major substrate for the gut microbiota that contributes to metabolic health. Recent studies have shown that diet–metabolic phenotype effect might be related to individual gut ...microbial profiles or enterotypes. Thus, the aim of this study was to examine whether microbial enterotypes modify the association between DF intake and metabolic traits. This cross-sectional study included 204 children (6–12 years old) and 75 adults (18–60 years old). Habitual DF intake was estimated with a Food Frequency Questionnaire and biochemical, clinical and anthropometric data were obtained. Gut microbiota was assessed through 16S sequencing and participants were stratified by enterotypes. Correlations adjusting for age and sex were performed to test the associations between dietary fiber components intake and metabolic traits. In children and adults from the Prevotella enterotype, a nominal negative correlation of hemicellulose intake with insulin and HOMA-IR levels was observed (p < 0.05), while in individuals of the other enterotypes, these associations were not observed. Interestingly, the latter effect was not related to the fecal short-chain-fatty acids profile. Our results contribute to understanding the enterotype influence on the diet–phenotype interaction, which ultimate could provide evidence for their use as potential biomarkers for future precision nutrition strategies.
Changes in the human gut microbiome are associated with obesity and metabolic syndrome, but the role of the gut virome in both diseases remains largely unknown. We characterized the gut dsDNA virome ...of 28 school-aged children with healthy normal-weight (NW, n = 10), obesity (O, n = 10), and obesity with metabolic syndrome (OMS, n = 8), using metagenomic sequencing of virus-like particles (VLPs) from fecal samples. The virome classification confirmed the bacteriophages' dominance, mainly composed of Caudovirales. Notably, phage richness and diversity of individuals with O and OMS tended to increase, while the VLP abundance remained the same among all groups. Of the 4,611 phage contigs composing the phageome, 48 contigs were highly prevalent in ≥80% of individuals, suggesting high inter-individual phage diversity. The abundance of several contigs correlated with gut bacterial taxa; and with anthropometric and biochemical parameters altered in O and OMS. To our knowledge, this gut phageome represents one of the largest datasets and suggests disease-specific phage alterations.
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•The VLP abundance remained the same between normal weight and obesity groups•Increased phage richness and diversity is linked to the disease•Bacteriophages dominated the gut virome with high inter-individual diversity•Differential phage abundances and prevalences are associated with the disease
Biological sciences; Physiology; Microbiology; Virology; Endocrinology; Omics.
The expression of facial asymmetries has been recurrently related with poverty and/or disadvantaged socioeconomic status. Departing from the developmental instability theory, previous approaches ...attempted to test the statistical relationship between the stress experienced by individuals grown in poor conditions and an increase in facial and corporal asymmetry. Here we aim to further evaluate such hypothesis on a large sample of admixed Latin Americans individuals by exploring if low socioeconomic status individuals tend to exhibit greater facial fluctuating asymmetry values. To do so, we implement Procrustes analysis of variance and Hierarchical Linear Modelling (HLM) to estimate potential associations between facial fluctuating asymmetry values and socioeconomic status. We report significant relationships between facial fluctuating asymmetry values and age, sex, and genetic ancestry, while socioeconomic status failed to exhibit any strong statistical relationship with facial asymmetry. These results are persistent after the effect of heterozygosity (a proxy for genetic ancestry) is controlled in the model. Our results indicate that, at least on the studied sample, there is no relationship between socioeconomic stress (as intended as low socioeconomic status) and facial asymmetries.
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