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Beta-2-glycoprotein 1 precursor (APC inhibitor) (Activated protein C-binding protein) (Anticardiolipin cofactor) (Apolipoprotein H) (Apo-H) (Beta-2-glycoprotein I) (B2GPI) (Beta(2)GPI) [B2G1]


Genome-wide significant results identified for plasma apolipoprotein H levels in middle-aged and older adults.

Apolipoprotein H (ApoH) is a multi-functional plasma glycoprotein that has been associated with negative health outcomes. ApoH levels have high heritability. We undertook a genome-wide association study of ApoH levels using the largest sample to date and replicated the results in an independent cohort (total N = 1,255). In the discovery phase, a meta-analysis of two cohorts, the Sydney Memory and Ageing Study (Sydney MAS) and the Older Australian Twins Study (OATS) (n = 942) revealed genome-wide significant results in or near the APOH gene on chromosome 17 (top SNP, rs7211380, p = 1 × 10(-11)). The results were replicated in an independent cohort, the Hunter Community Study (p < 0.002) (n = 313). Conditional and joint analysis (COJO) confirmed the association of the chromosomal 17 region with ApoH levels. The set of independent SNPs identified by COJO explained 23% of the variance. The relationships between the top SNPs and cardiovascular/lipid/cognition measures and diabetes were assessed in Sydney MAS, with suggestive results observed for diabetes and cognitive performance. However, replication of these results in the smaller OATS cohort was not found. This work provides impetus for future research to better understand the contribution of genetics to ApoH levels and its possible impacts on health.

MeSH Terms

  • Aged
  • Aged, 80 and over
  • Aging
  • Australia
  • Cardiovascular Diseases
  • Chromosomes, Human, Pair 17
  • Cognitive Dysfunction
  • Cohort Studies
  • Diabetes Mellitus
  • Female
  • Gene Expression
  • Genetic Loci
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • beta 2-Glycoprotein I

Exercise-induced oxidative stress in older adults as measured by antipyrine oxidation.

Aging is associated with increased susceptibility to free radical-mediated tissue damage. Measuring exercise-induced oxidative stress, however, is a major problem in free radical research. We used an exogenous marker (antipyrine) to measure oxidative stress in older adults during submaximal exercise. Antipyrine pharmacokinetics is independent of blood flow to the liver. Furthermore, antipyrine reacts quickly with hydroxyl radicals (10(10)-10(11) L x mol(-1) x s(-1)) to form para- and ortho-hydroxyantipyrine (o-APOH). o-APOH is not formed in man through the mono-oxygenase pathway of cytochrome P450. Thirty-four subjects (62 /- 1 years) orally ingested 10 mg antipyrine/kg body mass. One hour after ingestion subjects cycled 45 minutes at 50% maximal power output. Exercise significantly increased the ratio of para-hydroxyantipyrine (p-APOH) to native antipyrine in plasma (.0014 /-.0001 v.0021 /-.0002; P <.0001). Also, the ratio of o-APOH was significantly increased after exercise (.0014 /-.0001 v.0019 /-.0002; P <.0001). Exercise significantly increased plasma levels of plasma malondialdehyde MDA) (.55 /-.07 v.92 /-.21 micromol/L; P <.01). In conclusion, in older adults, oxidative stress occurs during cycling at submaximal intensity as measured with free radical reaction products of antipyrine.

MeSH Terms

  • Aging
  • Antipyrine
  • Bicycling
  • Exercise
  • Female
  • Free Radicals
  • Humans
  • Hydroxylation
  • Male
  • Malondialdehyde
  • Middle Aged
  • Oxidative Stress