The Journal of clinical endocrinology and metabolism · 2019
Novel Genetic Locus of Visceral Fat and Systemic Inflammation.
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Shin Jean, Syme Catriona, Wang Dominic, Richer Louis, Pike G Bruce, Gaudet Daniel, Paus Tomas, Pausova Zdenka
Аннотация
CONTEXT: Visceral fat (VF), more than fat elsewhere in the body [mostly subcutaneous fat (SF)], promotes systemic inflammation and related disease. The mechanisms of preferentially visceral accumulation of body fat are largely unknown.
OBJECTIVE: To identify genetic loci and mechanistic pathways of preferential accumulation of VF and associated low-grade systemic inflammation.
DESIGN: Genome-wide association study (GWAS).
SETTING AND PARTICIPANTS: Population-based cohort of 1586 adolescents (aged 12 to 19 years) and adults (aged 36 to 65 years).
MAIN OUTCOME MEASURES: Abdominal VF and SF were measured with MRI, total body fat (TBF) was assessed with bioimpedance, and low-grade systemic inflammation was examined by serum C-reactive protein (CRP) measurement.
RESULTS: This GWAS of preferential accumulation of VF identified a significant locus on chromosome 6 at rs803522 (P = 1.1 × 10-9 or 4.3 × 10-10 for VF adjusted for SF or TBF, respectively). The major allele was associated with more VF; the association was similar in adolescents and adults. The allele was also associated with higher CRP level, but this association was stronger in adults than adolescents (P for interaction = 4.5 × 10-3). In adults, VF was a significant mediator (P = 1.9× 10-4) in the association between the locus and CRP, explaining 30% of the mediation. The locus was near ATG5, encoding an autophagy molecule reported to modulate adipocyte size and macrophage polarization.
CONCLUSION: A genetic locus near ATG5 regulates preferential accumulation of VF (vs SF) in youth and adulthood and contributes to the development of systemic inflammation in adulthood.
OBJECTIVE: To identify genetic loci and mechanistic pathways of preferential accumulation of VF and associated low-grade systemic inflammation.
DESIGN: Genome-wide association study (GWAS).
SETTING AND PARTICIPANTS: Population-based cohort of 1586 adolescents (aged 12 to 19 years) and adults (aged 36 to 65 years).
MAIN OUTCOME MEASURES: Abdominal VF and SF were measured with MRI, total body fat (TBF) was assessed with bioimpedance, and low-grade systemic inflammation was examined by serum C-reactive protein (CRP) measurement.
RESULTS: This GWAS of preferential accumulation of VF identified a significant locus on chromosome 6 at rs803522 (P = 1.1 × 10-9 or 4.3 × 10-10 for VF adjusted for SF or TBF, respectively). The major allele was associated with more VF; the association was similar in adolescents and adults. The allele was also associated with higher CRP level, but this association was stronger in adults than adolescents (P for interaction = 4.5 × 10-3). In adults, VF was a significant mediator (P = 1.9× 10-4) in the association between the locus and CRP, explaining 30% of the mediation. The locus was near ATG5, encoding an autophagy molecule reported to modulate adipocyte size and macrophage polarization.
CONCLUSION: A genetic locus near ATG5 regulates preferential accumulation of VF (vs SF) in youth and adulthood and contributes to the development of systemic inflammation in adulthood.