A genome-wide association study in Caucasian women suggests the involvement of HLA genes in the severity of facial solar lentigines.
Solar lentigines are a common feature of sun-induced skin ageing. Little is known, however, about the genetic factors contributing to their development. In this genome-wide association study, we aimed to identify genetic loci associated with solar lentigines on the face in 502 middle-aged French women. Nine SNPs, gathered in two independent blocks on chromosome 6, exhibited a false discovery rate below 25% when looking for associations with the facial lentigine score. The first block, in the 6p22 region, corresponded to intergenic SNPs and also exhibited a significant association with forehead lentigines (P = 1.37 × 10(-8) ). The second block, within the 6p21 HLA region, was associated with decreased HLA-C expression according to several eQTL databases. Interestingly, these SNPs were also in high linkage disequilibrium with the HLA-C*0701 allele (r(2)  = 0.95). We replicated an association recently found by GWAS in the IRF4 gene. Finally, a complementary study on 44 selected candidate SNPs revealed novel associations in the MITF gene. Overall, our results point to several mechanisms involved in the severity of facial lentigines, including HLA/immunity and the melanogenesis pathway.
Équipe Génomique, Bioinformatique et Applications, Chaire de Bioinformatique, Conservatoire National des Arts et Métiers, Paris, France.
Vincent
V
Laville
Équipe Génomique, Bioinformatique et Applications, Chaire de Bioinformatique, Conservatoire National des Arts et Métiers, Paris, France.
Sigrid Le
SL
Clerc
UMR U557, INSERM/U1125 INRA/CNAM, University Paris 13/Centre de Recherche en Nutrition Humaine Ile-de-France, Bobigny, France.|Department of Dermatology, Hôpital Saint-André, Bordeaux, France.
Khaled
K
Ezzedine
Department of Skin Knowledge and Women Beauty, Chanel R&T, Pantin, France.
Randa
R
Jdid
Équipe Génomique, Bioinformatique et Applications, Chaire de Bioinformatique, Conservatoire National des Arts et Métiers, Paris, France.
Lieng
L
Taing
Équipe Génomique, Bioinformatique et Applications, Chaire de Bioinformatique, Conservatoire National des Arts et Métiers, Paris, France.
Taoufik
T
Labib
Équipe Génomique, Bioinformatique et Applications, Chaire de Bioinformatique, Conservatoire National des Arts et Métiers, Paris, France.
Cedric
C
Coulonges
Équipe Génomique, Bioinformatique et Applications, Chaire de Bioinformatique, Conservatoire National des Arts et Métiers, Paris, France.
Damien
D
Ulveling
Plate-forme Post-Génomique P3S, Hôpital Pitié-Salpêtrière, Paris, France.
Wassila
W
Carpentier
UMR U557, INSERM/U1125 INRA/CNAM, University Paris 13/Centre de Recherche en Nutrition Humaine Ile-de-France, Bobigny, France.
Pilar
P
Galan
UMR U557, INSERM/U1125 INRA/CNAM, University Paris 13/Centre de Recherche en Nutrition Humaine Ile-de-France, Bobigny, France.|Department of Public Health, Hôpital Avicenne, Bobigny, France.
Serge
S
Hercberg
Department of Skin Knowledge and Women Beauty, Chanel R&T, Pantin, France.
Frederique
F
Morizot
Department of Skin Knowledge and Women Beauty, Chanel R&T, Pantin, France.
Julie
J
Latreille
UMR U557, INSERM/U1125 INRA/CNAM, University Paris 13/Centre de Recherche en Nutrition Humaine Ile-de-France, Bobigny, France.|Department of Internal Medicine and Tropical Diseases, Hôpital Saint-André, Bordeaux, France.
Denis
D
Malvy
Department of Dermatology, University of Vienna Medical School, Vienna, Austria. erwin.tschachler@meduniwien.ac.at.
Erwin
E
Tschachler
Équipe Génomique, Bioinformatique et Applications, Chaire de Bioinformatique, Conservatoire National des Arts et Métiers, Paris, France. zagury@cnam.fr.
Jean-François
JF
Zagury
D015415:Biomarkers / Q000032:analysis; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006680:HLA Antigens / Q000235:genetics*; D006801:Humans; D007911:Lentigo / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D015810:Linkage Disequilibrium; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015595:Skin Aging / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D013472:Sunlight / Q000009:adverse effects*; D044465:White People
D015415:Biomarkers; D006680:HLA Antigens
HLA; HLA-C; SNP; genome-wide association study; skin ageing; solar lentigines