Department of Medicine, Jaume I University of Castellon, Castellon, Spain.
Department of Dermatology, Castellon University General Hospital, Castellon, Spain.
Photodermatol Photoimmunol Photomed. 2018 Nov;34(6):415-422. doi: 10.1111/phpp.12412. Epub 2018 Jul 25.
BACKGROUND/PURPOSE: Recent GWAS studies, mostly performed in populations of North European origin, have identified the genetic loci associated with pigmentation, sun sensitivity, freckling and skin cancer susceptibility. Here, we aimed at addressing the genetic determinants of sunlight sensitivity in Spain, a southern European population.
Nine SNPs located in 8 pigmentation-related genes (IRF4, TYR, ASP, HERC2, OCA2, BNC2, SLC24A4 and SLC45A2) were genotyped in 456 Spaniards. Additionally, the complete sequence of the MC1R gene was obtained, testing each nonsynonymous mutation supported by the classification as R or r alleles. A standardised questionnaire was used to collect demographic characteristics, pigmentation and sun sensitivity traits, as well as sun exposure habits.
MC1R R alleles and IRF4 rs12203592 were significantly associated with sunlight sensitivity at the Bonferroni-corrected level (P-value < 4.54 × 10 ). Genetic variants in SLC45A2 (rs16891982) and HERC2 (rs12913832) were also found to be significantly associated with skin photosensitivity in our Spanish sample. Interaction analysis using the MDR method revealed epistatic effects when these four variants were considered together.
MC1R, IRF4, HERC2 and SLC45A2 play a significant role in skin sensitivity to sunlight in the Spanish population. Moreover, interaction among these four loci seems to modulate the ability of the skin to respond to UV radiation.
背景/目的：最近的 GWAS 研究主要在北欧人群中进行，已确定了与肤色、日晒敏感性、雀斑和皮肤癌易感性相关的遗传位点。在这里，我们旨在研究西班牙（一个南欧人群）阳光敏感的遗传决定因素。
在 456 名西班牙人中，对 8 个与色素沉着相关基因（IRF4、TYR、ASP、HERC2、OCA2、BNC2、SLC24A4 和 SLC45A2）中的 9 个 SNP 进行了基因分型。此外，还获得了 MC1R 基因的完整序列，对每个非同义突变进行了测试，这些突变得到了 R 或 r 等位基因的分类支持。使用标准化问卷收集人口统计学特征、色素沉着和日晒敏感性特征以及日晒暴露习惯。
MC1R R 等位基因和 IRF4 rs12203592 在 Bonferroni 校正水平上与日晒敏感性显著相关（P 值<4.54×10-8）。在我们的西班牙样本中，SLC45A2（rs16891982）和 HERC2（rs12913832）中的遗传变异也与皮肤光敏性显著相关。使用 MDR 方法进行的交互分析显示，当同时考虑这四个变体时，存在上位性效应。
MC1R、IRF4、HERC2 和 SLC45A2 在西班牙人群的皮肤对阳光的敏感性中起重要作用。此外，这四个位点之间的相互作用似乎调节了皮肤对紫外线辐射的反应能力。
