Dataset Information

Interactions between SNP alleles at multiple Loci and variation in skin pigmentation in 122 Caucasians.

ABSTRACT: This study was undertaken to clarify the molecular basis for human skin color variation and the environmental adaptability to ultraviolet irradiation, with the ultimate goal of predicting the impact of changes in future environments on human health risk. One hundred twenty-two Caucasians living in Toledo, Ohio participated. Back and cheek skin were assayed for melanin as a quantitative trait marker. Buccal cell samples were collected and used for DNA extraction. DNA was used for SNP genotyping using the Masscode system, which entails two-step PCR amplification and a platform chemistry which allows cleavable mass spectrometry tags. The results show gene-gene interaction between SNP alleles at multiple loci (not necessarily on the same chromosome) contributes to inter-individual skin color variation while suggesting a high probability of linkage disequilibrium. Confirmation of these findings requires further study with other ethic groups to analyze the associations between SNP alleles at multiple loci and human skin color variation. Our overarching goal is to use remote sensing data to clarify the interaction between atmospheric environments and SNP allelic frequency and investigate human adaptability to ultraviolet irradiation. Such information should greatly assist in the prediction of the health effects of future environmental changes such as ozone depletion and increased ultraviolet exposure. If such health effects are to some extent predictable, it might be possible to prepare for such changes in advance and thus reduce the extent of their impact.

SUBMITTER: Anno S

PROVIDER: S-EPMC2684124 | biostudies-literature | 2007 Sep

REPOSITORIES: biostudies-literature

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Interactions between SNP alleles at multiple Loci and variation in skin pigmentation in 122 Caucasians.

Anno Sumiko S Abe Takashi T Sairyo Koichi K Kudo Susumu S Yamamoto Takushi T Ogata Koretsugu K Goel Vijay K VK

Evolutionary bioinformatics online 20070906

This study was undertaken to clarify the molecular basis for human skin color variation and the environmental adaptability to ultraviolet irradiation, with the ultimate goal of predicting the impact of changes in future environments on human health risk. One hundred twenty-two Caucasians living in Toledo, Ohio participated. Back and cheek skin were assayed for melanin as a quantitative trait marker. Buccal cell samples were collected and used for DNA extraction. DNA was used for SNP genotyping u ...[more]

PMID: 19461972

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Project description:Human pigmentation is a polygenic quantitative trait with high heritability. Although a large number of single nucleotide polymorphisms (SNPs) have been identified in pigmentation genes, very few SNPs have been examined in relation to human pigmentary phenotypes and skin cancer risk. We evaluated the associations between 15 SNPs in 8 candidate pigmentation genes (TYR, TYRP1, OCA2, SLC24A5, SLC45A2, POMC, ASIP and ATRN) and both pigmentary phenotypes (hair color, skin color and tanning ability) and skin cancer risk in a nested case-control study of Caucasians within the Nurses' Health Study (NHS) among 218 melanoma cases, 285 squamous cell carcinoma (SCC) cases, 300 basal cell carcinoma (BCC) cases and 870 common controls. We found that the TYR Arg402Gln variant was significantly associated with skin color (p-value = 7.7 x 10(-4)) and tanning ability (p-value = 7.3 x 10(-4)); the SLC45A2 Phe374Leu variant was significantly associated with hair color (black to blonde) (p-value = 2.4 x 10(-7)), skin color (p-value = 1.1 x 10(-7)) and tanning ability (p-value = 2.5 x 10(-4)). These associations remained significant after controlling for MC1R variants. No significant associations were found between these polymorphisms and the risk of skin cancer. We observed that the TYRP1 rs1408799 and SLC45A2 1721 C>G were associated with melanoma risk (OR, 0.77; 95% CI, 0.60-0.98 and OR, 0.75; 95% CI, 0.60-0.95, respectively). The TYR Ser192Tyr was associated with SCC risk (OR, 1.23; 95% CI, 1.00-1.50). The TYR haplotype carrying only the Arg402Gln variant allele was significantly associated with SCC risk (OR, 1.35; 95% CI, 1.04-1.74). The OCA2 Arg419Gln and ASIP g.8818 A>G were associated with BCC risk (OR, 1.50; 95% CI, 1.06-2.13 and OR, 0.73; 95% CI, 0.53-1.00, respectively). The haplotype near ASIP (rs4911414[T] and rs1015362[G]) was significantly associated with fair skin color (OR, 2.28; 95% CI, 1.46-3.57) as well as the risks of melanoma (OR, 1.68; 95% CI, 1.18-2.39) and SCC (OR, 1.54; 95% CI, 1.08-2.19). These associations remained similar after adjusting for pigmentary phenotypes and MC1R variants. The statistical power of our study was modest and additional studies are warranted to confirm the associations observed in the present study. Our study provides evidence for the contribution of pigmentation genetic variants, in addition to the MC1R variants, to variation in human pigmentary phenotypes and possibly the development of skin cancer.

Project description:A recent genome-wide association study (GWAS) in African descent populations identified novel loci associated with skin pigmentation. However, how genomic variations affect skin pigmentation and how these skin pigmentation gene variants affect serum 25(OH) vitamin D variation has not been explored in African Americans (AAs). In order to further understand genetic factors that affect human skin pigmentation and serum 25(OH)D variation, we performed a GWAS for skin pigmentation with 395 AAs and a replication study with 681 AAs. Then, we tested if the identified variants are associated with serum 25(OH) D concentrations in a subset of AAs (n = 591). Skin pigmentation, Melanin Index (M-Index), was measured using a narrow-band reflectometer. Multiple regression analysis was performed to identify variants associated with M-Index and to assess their role in serum 25(OH)D variation adjusting for population stratification and relevant confounding variables. A variant near the SLC24A5 gene (rs2675345) showed the strongest signal of association with M-Index (P = 4.0 x 10-30 in the pooled dataset). Variants in SLC24A5, SLC45A2 and OCA2 together account for a large proportion of skin pigmentation variance (11%). The effects of these variants on M-Index was modified by sex (P for interaction = 0.009). However, West African Ancestry (WAA) also accounts for a large proportion of M-Index variance (23%). M-Index also varies among AAs with high WAA and high Genetic Score calculated from top variants associated with M-Index, suggesting that other unknown genomic factors related to WAA are likely contributing to skin pigmentation variation. M-Index was not associated with serum 25(OH)D concentrations, but the Genetic Score was significantly associated with vitamin D deficiency (serum 25(OH)D levels less than 12 ng/mL) (OR, 1.30; 95% CI, 1.04-1.64). The findings support the hypothesis suggesting that skin pigmentation evolved responding to increased demand for subcutaneous vitamin D synthesis in high latitude environments.

Dataset Information

Interactions between SNP alleles at multiple Loci and variation in skin pigmentation in 122 Caucasians.

Publications

Interactions between SNP alleles at multiple Loci and variation in skin pigmentation in 122 Caucasians.

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