title: Genetic association study of common mitochondrial variants on body fat mass.
abstract: Mitochondria play a central role in ATP production and energy metabolism. Previous studies suggest that common variants in mtDNA are associated with several common complex diseases, including obesity. To test the hypothesis that common mtDNA variants influence obesity-related phenotypes, including BMI and body fat mass, we genotyped a total of 445 mtSNPs across the whole mitochondrial genome in a large sample of 2,286 unrelated Caucasian subjects. 72 of these 445 mtSNPs passed quality control criteria, and were used for subsequent analyses. We also classified all subjects into nine common European haplogroups. Association analyses were conducted for both BMI and body fat mass with single mtSNPs and mtDNA haplogroups. Two mtSNPs, mt4823 and mt8873 were detected to be significantly associated with body fat mass, with adjusted P values of 4.94 × 10⁻³ and 4.58 × 10⁻², respectively. The minor alleles mt4823 C and mt8873 A were associated with reduced fat mass values and the effect size (β) was estimated to be 3.52 and 3.18, respectively. These two mtSNPs also achieved nominally significant levels for association with BMI. For haplogroup analyses, we found that haplogroup X was strongly associated with both BMI (adjusted P = 8.31 × 10⁻³) and body fat mass (adjusted P = 5.67×10⁻⁴) Subjects classified as haplogroup X had lower BMI and fat mass values, with the β estimated to be 2.86 and 6.03, respectively. Our findings suggest that common variants in mitochondria might play a role in variations of body fat mass. Further molecular and functional studies will be needed to clarify the potential mechanism.
authors: Key Laboratory of Biomedical Information Engineering of Ministry of Education, and Institute of Molecular Genetics, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China.
authors: Tie-Lin
authors: TL
authors: Yang
authors: Yan
authors: Y
authors: Guo
authors: Hui
authors: H
authors: Shen
authors: Shu-Feng
authors: SF
authors: Lei
authors: Yong-Jun
authors: YJ
authors: Liu
authors: Jian
authors: J
authors: Li
authors: Yao-Zhong
authors: YZ
authors: Liu
authors: Na
authors: N
authors: Yu
authors: Jia
authors: J
authors: Chen
authors: Ting
authors: T
authors: Xu
authors: Yu
authors: Y
authors: Cheng
authors: Qing
authors: Q
authors: Tian
authors: Ping
authors: P
authors: Yu
authors: Christopher J
authors: CJ
authors: Papasian
authors: Hong-Wen
authors: HW
authors: Deng
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D015992:Body Mass Index; D004272:DNA, Mitochondrial / Q000235:genetics; D005260:Female; D054629:Genome, Mitochondrial / Q000235:genetics; D055106:Genome-Wide Association Study; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000235:genetics*; D009765:Obesity / Q000235:genetics / Q000503:physiopathology; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011786:Quality Control; D044465:White People / Q000235:genetics
chemical_list: D004272:DNA, Mitochondrial