ArticleObesity (Silver Spring, Md.)2011
Replication and extension of association between common genetic variants in SIM1 and human adiposity.
Article in Obesity (Silver Spring, Md.), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 2 of them syntheses that pooled it.
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Who cites it
14 citing papers in PubMed, 2 syntheses or guidelines pooled it, 23 citations in OpenAlex.
- Systematic review: pain, cognition, and cardioprotection-unpacking oxytocin's contributions in a sport context.Frontiers in physiology · 2024Pooled it
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- The hypothalamus for whole-body physiology: from metabolism to aging.Protein & cell · 2022Review
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- Microarray Analysis of lncRNA and mRNA Reveals Enhanced Lipolysis Along With Metabolic Remodeling in Mice Infected With LarvalFrontiers in physiology · 2020Article
- In vivo measurements reveal a single 5'-intron is sufficient to increase protein expression level in Caenorhabditis elegans.Scientific reports · 2019Article
- Emotion recognition associated with polymorphism in oxytocinergic pathway gene ARNT2.Social cognitive and affective neuroscience · 2018Article
- Genetic analysis of single-minded 1 gene in early-onset severely obese children and adolescents.PloS one · 2017Article
- Article
- Chronic oxytocin administration inhibits food intake, increases energy expenditure, and produces weight loss in fructose-fed obese rhesus monkeys.American journal of physiology. Regulatory, integrative and comparative physiology · 2015Article
- From Autism to Eating Disorders and More: The Role of Oxytocin in Neuropsychiatric Disorders.Frontiers in neuroscience · 2015Review
- Mutation screen of the SIM1 gene in pediatric patients with early-onset obesity.International journal of obesity (2005) · 2014Article
- Role of oxytocin signaling in the regulation of body weight.Reviews in endocrine & metabolic disorders · 2013Review
- Coming full circle: contributions of central and peripheral oxytocin actions to energy balance.Endocrinology · 2013Review
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
Haplo-insufficiency of the bHLH (basic helix-loop-helix) transcription factor single-minded 1 (SIM1) causes severe obesity in mice and humans. We hypothesized that common genetic variations in/near SIM1 could exert more subtle effects on its function and associate with human adiposity. First, SIM1 coding regions were sequenced in severely obese subjects, and two common nonsynonymous single-nucleotide polymorphisms (nsSNPs) in complete linkage disequilibrium (LD) were identified: Pro352Thr (rs3734354) and Ala371Val (rs3734355). We next carried out a SNP association study of five adiposity traits (BMI, % body fat, abdominal visceral and subcutaneous fat, and leptin concentrations) in 1,699 whites and 1,173 blacks. TagSNPs covering SIM1 and nearby conserved regions, and the only common nsSNP in SIM1's binding partner aryl-hydrocarbon receptor nuclear translocator 2 (ARNT2) (Gly679Ser/rs4072568), were investigated. The effects of rs3734355/4 on SIM1 activity were tested using an in vitro reporter assay. We replicated previous observations that homozygosity for the 371Val allele was associated with higher BMI in white males (P = 0.003). Together with previous findings in white males (combined n = 3,479), BMI was increased by 1.10 kg/m(2) in 371Val homozygotes (95% confidence interval (CI): 0.25-1.95 kg/m(2), P = 0.01). In vitro, the 352Thr-371Val haplotype impaired SIM1 transcriptional activity by 22% (P < 0.0001). TagSNP analysis of SIM1 revealed two SNPs in the 3' region (rs9390322 and rs7746743) and another in intron 5 (rs3734353) to be significantly associated with various adiposity measures in ethnicity- and sex-specific manners after multiple testing correction. In white males, rs4072568 in ARNT2 was also associated with BMI (P = 9 × 10(-4)) and % body fat (P = 0.001). Our findings implicate heritable defects of the SIM1-ARNT2 axis in the predisposition to human obesity.
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