title: Single nucleotide polymorphisms in the mitochondrial control region are associated with metabolic phenotypes and oxidative stress.
abstract: OBJECTIVE
  To identify the mitochondrial DNA (mtDNA) single nucleotide polymorphisms (SNPs) in the control region and elucidate their role in metabolic phenotypes and oxidative stress.
  
  
  METHODS
  A total of 861 nondiabetic subjects were enrolled, including 250 impaired fasting glucose (IFG) and 370 obese subjects (body mass index [BMI]>25 kg/m(2)). Antioxidant status presented as total free thiol level was determined from serum samples. DNA was extracted from peripheral blood leucocytes, and the sequences were analyzed using the DNASTAR software. SNPs were identified by comparison with the Cambridge Reference Sequence.
  
  
  RESULTS
  After adjusting odds ratios for age, sex, and BMI, the selected independently significant SNPs indicated 4 susceptible SNPs: SNP-16126C and SNP-16261T, which were related to abdominal obesity (P=0.009; 0.06); SNP-16390A, related to hypertension (HTN) (P=0.007); and SNP-16092C, related to decreased antioxidant capacity (P=0.015). In the obese subgroup, 3 susceptible SNPs included SNP-16189C and SNP-16260T, which showed significantly higher IFG prevalence (P=0.016 and 0.024, respectively), and SNP-16519C, which was significantly higher in the HTN group (P=0.036). As to protective SNPs, 5 protective SNPs were identified in all subjects but only one SNP-16093C is consistent in obese group, which showed a significantly lower prevalence in patients with abdominal obesity and was associated with a higher antioxidant status (P<0.001).
  
  
  CONCLUSIONS
  SNPs in the mtDNA control region are associated with metabolic phenotypes and oxidative stress markers. Some SNPs are relating to the interaction between obesity and genetic factors. The beneficial effects of these protective SNPs were insignificant and some susceptible SNPs became dominant within the obese subgroup. Subjects harboring these SNPs should avoid excessive weight gain.
authors: Department of Internal Medicine, Mitochondrial Research Unit, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors: Shao-Wen
authors: SW
authors: Weng
authors: Tsu-Kung
authors: TK
authors: Lin
authors: Pei-Wen
authors: PW
authors: Wang
authors: Shang-Der
authors: SD
authors: Chen
authors: Yao-Chung
authors: YC
authors: Chuang
authors: Chia-Wei
authors: CW
authors: Liou
mesh_terms: D000328:Adult; D000368:Aged; D015992:Body Mass Index; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D019901:Locus Control Region / Q000235:genetics*; D008297:Male; D008659:Metabolic Diseases / Q000235:genetics*; D008875:Middle Aged; D009765:Obesity / Q000150:complications / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000502:physiology
chemical_list: D004272:DNA, Mitochondrial
keywords: AO; BMI; HTN; Hypertension; IFG; Impaired fasting glucose; Mitochondrial SNPs; Obesity; Oxidative stress; SNPs; TBARS; abdominal obesity; body mass index; hypertension; impaired fasting glucose; mitochondrial DNA; mtDNA; single nucleotide polymorphisms; thiobarbituric acid reactive substance