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PubMed · 7618162

Radical differences in CYP1A1 genotype and function.

E Taioli·F Crofts·J Trachman·S Bayo·P Toniolo·S J Garte
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Abstract

The cytochrome P450 1A1 (CYP1A1) gene may be of critical importance in determining individual cancer susceptibility to aromatic hydrocarbons such as those in tobacco smoke. We compared the frequencies of CYP1A1 haplotypes, and complete genotypes, taking into account polymorphisms at 3 sites, including an African-specific polymorphism. No concordance was observed in Africans or African-Americans between any of the 3 polymorphisms, (Msp1 restriction fragment length polymorphism (RFLP)--'M', exon 7--'E', new RFLP--'A') in contrast to the concordance seen between the M and E polymorphisms in Caucasians and Asians. We observed an effect of the E polymorphism on enzyme activity and mRNA induction in Asians and Caucasians.

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Asian PeopleBase SequenceBlack PeopleCytochrome P-450 Enzyme SystemGenetics, PopulationGenotypeHumansMolecular Sequence DataPolymorphism, GeneticRacial GroupsWhite PeopleBlack or African AmericanJournal ArticleResearch Support, U.S. Gov't, P.H.S.

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E Taioli, F Crofts, J Trachman, S Bayo, P Toniolo, S J Garte. 1995. Radical differences in CYP1A1 genotype and function.. https://doi.org/10.1016/0378-4274(95)03318-1

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Signatures of positive selection in genes associated with human skin pigmentation as revealed from analyses of single nucleotide polymorphisms.

Phenotypic variation between human populations in skin pigmentation correlates with latitude at the continental level. A large number of hypotheses involving genetic adaptation have been proposed to explain human variation in skin colour, but only limited genetic evidence for positive selection has been presented. To shed light on the evolutionary genetic history of human variation in skin colour we inspected 118 genes associated with skin pigmentation in the Perlegen dataset, studying single nucleotide polymorphisms (SNPs), and analyzed 55 genes in detail. We identified eight genes that are associated with the melanin pathway (SLC45A2, OCA2, TYRP1, DCT, KITLG, EGFR, DRD2 and PPARD) and presented significant differences in genetic variation between Europeans, Africans and Asians. In six of these genes we detected, by means of the EHH test, variability patterns that are compatible with the hypothesis of local positive selection in Europeans (OCA2, TYRP1 and KITLG) and in Asians (OCA2, DCT, KITLG, EGFR and DRD2), whereas signals were scarce in Africans (DCT, EGFR and DRD2). Furthermore, a statistically significant correlation between genotypic variation in four pigmentation candidate genes and phenotypic variation of skin colour in 51 worldwide human populations was revealed. Overall, our data also suggest that light skin colour is the derived state and is of independent origin in Europeans and Asians, whereas dark skin color seems of unique origin, reflecting the ancestral state in humans.

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