A genome-wide association study identifies novel gene associations with facial skin wrinkling and mole count in Latin Americans.

BACKGROUND: Genome-wide association studies (GWASs) have identified genes influencing skin ageing and mole count in Europeans, but little is known about the relevance of these (or other genes) in non-Europeans. OBJECTIVES: To conduct a GWAS for facial skin ageing and mole count in adults < 40 years old, of mixed European, Native American and African ancestry, recruited in Latin America. METHODS: Skin ageing and mole count scores were obtained from facial photographs of over 6000 individuals. After quality control checks, three wrinkling traits and mole count were retained for genetic analyses. DNA samples were genotyped with Illumina's HumanOmniExpress chip. Association testing was performed on around 8 703 729 single-nucleotide polymorphisms (SNPs) across the autosomal genome. RESULTS: Genome-wide significant association was observed at four genome regions: two were associated with wrinkling (in 1p13·3 and 21q21·2), one with mole count (in 1q32·3) and one with both wrinkling and mole count (in 5p13·2). Associated SNPs in 5p13·2 and in 1p13·3 are intronic within SLC45A2 and VAV3, respectively, while SNPs in 1q32·3 are near the SLC30A1 gene, and those in 21q21·2 occur in a gene desert. Analyses of SNPs in IRF4 and MC1R are consistent with a role of these genes in skin ageing. CONCLUSIONS: We replicate the association of wrinkling with variants in SLC45A2, IRF4 and MC1R reported in Europeans. We identify VAV3 and SLC30A1 as two novel candidate genes impacting on wrinkling and mole count, respectively. We provide the first evidence that SLC45A2 influences mole count, in addition to variants in this gene affecting melanoma risk in Europeans.

Trimethylamine N-oxide levels are associated with NASH in obese subjects with type 2 diabetes.

AIMS: Trimethylamine N-oxide (TMAO), choline and betaine serum levels have been associated with metabolic diseases including type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD). These associations could be mediated by insulin resistance. However, the relationships among these metabolites, insulin resistance and NAFLD have not been thoroughly investigated. Moreover, it has recently been suggested that TMAO could play a role in NAFLD by altering bile acid metabolism. We examined the association between circulating TMAO, choline and betaine levels and NAFLD in obese subjects. METHODS: Serum TMAO, choline, betaine and bile acid levels were measured in 357 Mexican obese patients with different grades of NAFLD as determined by liver histology. Associations of NAFLD with TMAO, choline and betaine levels were tested. Moreover, association of TMAO levels with non-alcoholic steatohepatitis (NASH) was tested separately in patients with and without T2D. RESULTS: TMAO and choline levels were significantly associated with NAFLD histologic features and NASH risk. While increased serum TMAO levels were significantly associated with NASH in patients with T2D, in non-T2D subjects this association lost significance after adjusting for sex, BMI and HOMA2-IR. Moreover, circulating secondary bile acids were associated both with increased TMAO levels and NASH. CONCLUSIONS: In obese patients, circulating TMAO levels were associated with NASH mainly in the presence of T2D. Functional studies are required to evaluate the role of insulin resistance and T2D in this association, both highly prevalent in NASH patients.

Composition of gut microbiota in obese and normal-weight Mexican school-age children and its association with metabolic traits.

BACKGROUND: Childhood obesity is a serious public health problem in Mexico. Adult gut microbiota composition has been linked to obesity, but few studies have addressed the role of gut microbiota in childhood obesity. OBJECTIVES: The aim of this study is to compare gut microbiota composition in obese and normal-weight children and to associate gut microbiota profiles with amino acid serum levels and obesity-related metabolic traits. METHODS: Microbial taxa relative abundance was determined by 16S rRNA sequencing in 67 normal-weight and 71 obese children aged 6-12 years. Serum amino acid levels were measured by mass spectrometry. Associations between microbiota composition, metabolic parameters and amino acid serum levels were tested. RESULTS: No significant differences in phyla abundances or Firmicutes/Bacteroidetes ratios were observed between normal-weight and obese children. However, Bacteroides eggerthii abundance was significantly higher in obese children and correlated positively with body fat percentage and negatively with insoluble fibre intake. Additionally, Bacteroides plebeius and unclassified Christensenellaceae abundances were significantly higher in normal-weight children. Abundance of both these species correlated negatively with phenylalanine serum levels, a metabolite also found to be associated with obesity in Mexican children. CONCLUSIONS: The study identified bacterial species associated with obesity, metabolic complications and amino acid serum levels in Mexican children.