Genotypes for the cytochrome P450 enzymes CYP2D6 and CYP2C19 in human longevitY. Role of CYP2D6 and CYP2C19 in longevity.

Authors: Bathum L; Andersen-Ranberg K; Boldsen J; Brøsen K; Jeune B

Abstract: OBJECTIVE: To test whether some genotypes for CYP2D6 or CYP2C19 could contribute to longevity, we genotyped 241 Danish nonagenarians and centenarians for CYP2D6 and CYP2C19. METHODS: For CYP2D6 we identified the alleles CYP2D6*1, CYP2D6*3 and CYP2D6*4 with allele-specific polymerase chain reaction (PCR). The CYP2D6*5 alleles were identified with a long PCR method. For CYP2C19 we identified the alleles CYP2C19*1, CYP2C19*2 and CYP2C19*3 with an oligonucleotide ligation assay. RESULTS: The four alleles for CYP2D6 did not occur in Hardy-Weinberg proportions. The frequency of poor metabolism was slightly higher (10.2%) than expected [7.7%; odds ratio (OR) = 1.36 (0.75-2.40)]. The genotypes for CYP2C19 occur in Hardy-Weinberg proportions. The frequency of poor metabolism (3.8%) was not significantly different from a young control group [3.1%; OR = 1.21 (0.26-5.75)]. CONCLUSION: CYP2D6 could play a role in human longevity due to the lack of Hardy-Weinberg proportions. If CYP2D6 only plays a role in longevity by protecting the poor metabolizers from cancer, we should expect a rise in the frequency in these genotypes in Denmark from 7.7% among young adults to 10-11% among very old people. We found a frequency of poor metabolism of 10.2% in the very old group. CYP2C19 is - due to the occurrence of Hardy-Weinberg proportions and the expected number of poor metabolizers unlikely to contribute to human longevity.

Keywords: Adult; Aged; Aged, 80 and over; Aging/*physiology; Alleles; *Aryl Hydrocarbon Hydroxylases; Cytochrome P-450 CYP2D6/*genetics/metabolism; Cytochrome P-450 Enzyme System/*genetics/metabolism; DNA/genetics; Female; Genotype; Humans; *Longevity; Male; Middle Aged; Mixed Function Oxygenases/*genetics/metabolism
Journal: European journal of clinical pharmacology
Volume: 54
Issue: 5
Pages: 427-30
Date: Oct. 1, 1998
PMID: 9754988
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Citation:

Bathum L, Andersen-Ranberg K, Boldsen J, Brøsen K, Jeune B (1998) Genotypes for the cytochrome P450 enzymes CYP2D6 and CYP2C19 in human longevitY. Role of CYP2D6 and CYP2C19 in longevity. European journal of clinical pharmacology 54: 427-30.


Longevity Variant Associations (p-value):
  • rs3892097, rs35742686, rs1135824, rs35742686 (0.05)
  • CYP2C19*1 (wt allele) / CYP2C19*2( rs4244285 / rs17878459 ) (0.2)

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