Association of the SLC45A2 gene with physiological human hair colour variation

Abstract

Pigmentation is a complex physical trait with multiple genes involved. Several genes have already been associated with natural differences in human pigmentation. The SLC45A2 gene encoding a transporter protein involved in melanin synthesis is considered to be one of the most important genes affecting human pigmentation. Here we present results of an association study conducted on a population of European origin, where the relationship between two non-synonymous polymorphisms in the SLC45A2 gene -rs26722 (E272K) and rs16891982 (L374F) -and different pigmentation traits was examined. The study revealed a significant association between both variable sites and normal variation in hair colour. Only L374F remained significantly associated with hair colour when both SNPs were included in a logistic regression model. No association with other pigmentation traits was detected in this population sample. Our results indicate that the rare allele L374 significantly increases the possibility of having black hair colour (OR = 7.05) and thus may be considered as a future marker for black hair colour prediction.

Colorful DNA polymorphisms in humans

“…In humans, SLC45A2 mutations are known to cause oculocutaneous albinism type 4 (OCA4) [137][138][139]. Common SNPs, including two non-synonymous SNPs in SLC45A2, rs16891982 (L374F, c.1122G>C) and rs26722 (E272K, c.814G>A), have been associated with normal variation in human skin, hair, and eye color in Europeans, South Asians, as well as in admixed individuals [126,[140][141][142][143]. The association of rs26722 may be explained by linkage disequilibrium with rs16891982 [142].…”

“…Common SNPs, including two non-synonymous SNPs in SLC45A2, rs16891982 (L374F, c.1122G>C) and rs26722 (E272K, c.814G>A), have been associated with normal variation in human skin, hair, and eye color in Europeans, South Asians, as well as in admixed individuals [126,[140][141][142][143]. The association of rs26722 may be explained by linkage disequilibrium with rs16891982 [142]. The derived 374F allele is almost fixed in people of European descent, highly frequent in Uygurs from Urumqi (west China), and quite rare in the other populations examined [141,144].…”

Screening study for genetic polymorphisms affecting pharmacokinetics of simvastatin

“…The SLC45A2 gene, which encodes a transporter protein involved in melanin synthesis, is considered one of the most important genes affecting human pigmentation. [24] Our results showed that minor allele homozygotes (A) of rs35390 of SLC45A2 might beassociated (P = 0.007 and P = 8.877x10 -5 , in additive and recessive models, respectively; Table 5) with an increased absorption of simvastatin. SLC25A37 (Mitoferrin-1; Mfrn1), a member of the solute carrier family localized in the mitochondrial inner membrane, functions as an essential iron importer for the synthesis of mitochondrial heme and iron-sulfur clusters in erythroblasts.…”

Genetic Differences between Five European Populations

“…Some genes implicated before in the genetics of hair and skin color did not reach our 11 most significant hits, but were also strongly stratified: TYR (tyrosinase precursor) [20] [16,19,21] , reached p = 3.1 ! 10 -36 .…”