Association between T102C 5-HT2A receptor gene polymorphism and 5-year mortality risk among Brazilian Amazon riparian elderly population

Am J Hum Biol. 2017 Sep 10;29(5). doi: 10.1002/ajhb.23016. Epub 2017 May 10.

Abstract

Objective: Serotonin (5-HT) is a pleiotropic molecule that exerts several functions on brain and peripheral tissues via different receptors. The gene for the 5-HT2A receptor shows some variations, including a T102C polymorphism, that have been associated with increased risk of neuropsychiatric and vascular disorders. However, the potential impact of 5-HT2A imbalance caused by genetic variations on the human lifespan has not yet been established.

Methods: We performed a prospective study involving an Amazon riparian elderly free-living population in Maués City, Brazil, with a 5-year follow-up. Out of a cohort of 637 subjects selected in July, 2009, we genotyped 471 individuals, including 209 males (44.4%) and 262 females (55.6%), all averaging 72.3 ± 7.8 years of age (ranging from 60 to 100 years).

Results: The T102C-SNP genotypic frequencies were 14.0% TT, 28.0% CC, and 58.0% CT. From 80 elderly individuals who died during the period investigated, we observed significantly (P = .005) higher numbers of TT carriers (27.3%) and CC carriers (21.2%), compared to heterozygous CT carriers (12.5%). Cox-regression analysis showed that association between the T102C-SNP and elderly survival was independent of age, sex, and other health variables.

Conclusions: Our findings strongly suggest that imbalance in 5-HT2A may cause significant disturbances that lead to an increased susceptibility to death for individuals who are over 60 years of age.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Brazil
  • Cities
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mortality*
  • Polymorphism, Genetic*
  • Prospective Studies
  • Receptor, Serotonin, 5-HT2A / genetics*
  • Receptor, Serotonin, 5-HT2A / metabolism
  • Risk

Substances

  • Receptor, Serotonin, 5-HT2A