Implications of Central Obesity-Related Variants in LYPLAL1, NRXN3, MSRA, and TFAP2B on Quantitative Metabolic Traits in Adult Danes

abstract: ...Background Two meta-analyses of genome-wide association studies (GWAS) have suggested that four variants: rs2605100 in lysophospholipase-like 1 (LYPLAL1), rs10146997 in neuroxin 3 ( NRXN3), rs545854 in methionine sulfoxide reductase A (MSRA), and rs987237 in transcription factor activating enhancer-binding protein 2 beta ( TFAP2B) associate with measures of central obesity. To elucidate potential underlying phenotypes we aimed to investigate whether these variants associated with: 1) quantitative metabolic traits, 2) anthropometric measures (waist circumference (WC), waist-hip ratio, and BMI), or 3) type 2 diabetes, and central and general overweight and obesity. Methodology/Principal Findings The four variants were genotyped in Danish individuals using KASPar. Quantitative metabolic traits were examined in a population-based sample (n =6,038) and WC and BMI were furthermore analyzed in a combined study sample ( n =13,507). Case-control studies of diabetes and adiposity included 15,326 individuals. The major G-allele of LYPLAL1 rs2605100 associated with increased fasting serum triglyceride concentrations (per allele effect ()=3%(1;5(95%CI)), p additive =2.710 3 ), an association driven by the male gender ( p interaction =0.02). The same allele associated with increased fasting serum insulin concentrations (=3%(1;5), p additive =2.510 3 ) and increased insulin resistance (HOMA-IR) (=4%(1;6), p additive =1.510 3 ). The minor G-allele of rs10146997 in NRXN3 associated with increased WC among women (=0.55cm (0.20;0.89), p additive =1.710 3 , p interaction =1.010 3 ), but showed no associations with obesity related metabolic traits. The MSRA rs545854 and TFAP2B rs987237 showed nominal associations with central obesity; however, no underlying metabolic phenotypes became obvious, when investigating quantitative metabolic traits. None of the variants influenced the prevalence of type 2 diabetes. Conclusion/Significance We demonstrate that several of the central obesity-associated variants in LYPLAL1, NRXN3, MSRA , and TFAP2B associate with metabolic and anthropometric traits in Danish adults. However, analyses were made without adjusting for multiple testing, and further studies are needed to confirm the putative role of LYPLAL1 , NRXN3, MSRA , and TFAP2B in the pathophysiology of obesity.

...PLoS One plos plosone PLoS ONE 1932-6203 Public Library of Science San Francisco, USA 21674055 3107232 PONE-D-11-00971 10.1371/journal.pone.0020640 Research Article Biology Genetics Human Genetics Genetic Association Studies Implications of Central Obesity-Related Variants in LYPLAL1, NRXN3, MSRA, and TFAP2B on Quantitative Metabolic Traits in Adult Danes Obesity-Related Variants and Metabolic Traits Bille Dorthe S. 1 2 3 Banasik Karina 1 * Justesen Johanne M. 1 Sandholt Camilla H. 1 4 Sandbk

..., distribution, and reproduction in any medium, provided the original author and source are credited. 2011 Background Two meta-analyses of genome-wide association studies (GWAS) have suggested that four variants: rs2605100 in lysophospholipase-like 1 (LYPLAL1), rs10146997 in neuroxin 3 ( NRXN3), rs545854 in methionine sulfoxide reductase A (MSRA), and rs987237 in transcription factor activating enhancer-binding protein 2 beta ( TFAP2B) associate with measures of central obesity. To elucidate potential

... combined study sample ( n =13,507). Case-control studies of diabetes and adiposity included 15,326 individuals. The major G-allele of LYPLAL1 rs2605100 associated with increased fasting serum triglyceride concentrations (per allele effect ()=3%(1;5(95%CI)), p additive =2.710 3 ), an association driven by the male gender ( p interaction =0.02). The same allele associated with increased fasting serum insulin concentrations (=3%(1;5), p additive =2.510 3 ) and increased insulin resistance (HOMA-IR) (=4

... diabetes. Conclusion/Significance We demonstrate that several of the central obesity-associated variants in LYPLAL1, NRXN3, MSRA , and TFAP2B associate with metabolic and anthropometric traits in Danish adults. However, analyses were made without adjusting for multiple testing, and further studies are needed to confirm the putative role of LYPLAL1 , NRXN3, MSRA , and TFAP2B in the pathophysiology of obesity. Introduction Obesity is a major health problem with increasing prevalence in Western societies

.... Following, two meta-analyses demonstrated four loci to associate with measures of central adiposity (waist circumference (WC) and waisthip-ratio (WHR)): 1) a meta-analysis of 16 GWAS ( n =38,580) with follow-up studies in a maximum of 118,691 individuals of European origin, identified variants near lysophospholipase-like 1 (LYPLAL1), methionine sulfoxide reductase A (MSRA), and transcription factor activating enhancer-binding protein 2 beta (TFAP2B), to strongly associate with measures of central adiposity using information about adult WC and WHR [8] , and 2) a large-scale meta-analysis of GWAS from the CHARGE Consortium involving 70,014 Caucasian individuals identified neuroxin 3 ( NRXN3) as a novel locus for central adiposity [9] . Lysophospholipase-like 1 protein, encoded by LYPLAL1, is thought to act as a triglyceride lipase and reported to be up-regulated in subcutaneous adipose tissue of obese individuals [10] . In the meta-analysis of 16 GWAS, the major G-allele of rs2605100 in LYPLAL1

... candidates for obesity, the causal variants and their role in the pathogenesis of obesity remain to be elucidated. The aim of the present study was to investigate central obesity-associated variants in LYPLAL1, NRXN3, MSRA , and TFAP2B for associations with quantitative metabolic traits in a population-based sample of 6,038 adult Danes (The Inter99 study sample). In addition, we examined associations between these variants and anthropometric measures (WC, WHR, and BMI) in a larger group of individuals

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Gene: LYPLAL1 - lysophospholipase-like 1 - (NCBI)

Protein : 3u0v

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