Polymorphisms of caffeine metabolism and estrogen receptor genes and risk of Parkinson's disease in men and women

Parkinsonism Relat Disord. 2010 Jul;16(6):370-5. doi: 10.1016/j.parkreldis.2010.02.012. Epub 2010 Mar 20.

Abstract

Caffeine intake has been associated with a decreased risk of Parkinson's disease (PD) in men but the effect in women is less clear, and appears to be modified by use of post-menopausal estrogens. In a nested case-control study within the Nurses Health Study (NHS) and the Health Professionals Follow-up Study (HPFS), we examined associations between single nucleotide polymorphisms (SNPs) of caffeine metabolizing genes (CYP1A2 and NAT2) and estrogen receptors (ESR1 and ESR2), their interaction with caffeine intake and hormone replacement therapy (PMH) use (collected prospectively) and risk of PD. We matched 159 female cases to 724 controls and 139 male cases to 561 controls on birth year, source of DNA (blood or buccal smear), age and sex. The CYP1A2 rs762551 polymorphism (lower enzyme inducibility) was marginally associated with an increased risk of PD (RR, for increasing number of minor alleles=1.34; 95% CI 1.02, 1.78 in women, but not in men. None of the NAT2 (classified as slow vs. fast acetylator), ESR1 or ESR2 polymorphisms were significantly associated with an altered risk of PD. Marginally significant interactions were observed between caffeine intake and the ESR1 polymorphism rs3798577 (p=0.07) and ESR2 polymorphism rs1255998 (p=0.07). The observed increased risk of PD among female but not male carriers of the rs762551 polymorphism of CYP1A2 and the interactions of caffeine with ESR1 rs3798577 and ESR2 rs1255998 may provide clues to explain the relationship between gender, caffeine intake, estrogen status and risk of PD and need to be replicated.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Caffeine / metabolism*
  • Case-Control Studies
  • Cytochrome P-450 CYP1A2 / genetics
  • Estrogen Replacement Therapy / adverse effects
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Male
  • Parkinson Disease / genetics*
  • Parkinson Disease / metabolism*
  • Polymorphism, Single Nucleotide*
  • Receptors, Estrogen / genetics*
  • Risk Factors
  • Sex Distribution

Substances

  • Receptors, Estrogen
  • Caffeine
  • Cytochrome P-450 CYP1A2