The Association Between MC1R Polymorphism And Clinico-Dermoscopic Features Of Acquired Pigmented Nevus In Chinese Han Population

BackgroundDermoscopy is a well-established non-invasive approach in the diagnosis and differential diagnosis of melanocytic and non-melanocytic lesions with high accuracy and specialty than clinical examination with naked eye. Human Melanocortin 1 receptor(MC1R) gene is highly polymorphic gene, coding for seven transmembrane G proteins, combined with specific ligands and through a series of reaction, then finally produce eumelanin or pheomelanin. To date, the existing research shows that the MC1 R gene polymorphism is associated with pigment phenotype(skin, hair, eyes and freckles) and skin cancer(malignant melanoma, squamous cell carcinoma, basal cell carcinoma). The association betweem MC1 R polymorphism and clinico-dermoscopic features of acquired pigmented nevus in Chinese Han population has not been reported. ObjectiveStudy the association between MC1 R polymorphism and clinico-dermoscopic features of acquired pigmented nevus in Chinese Han population. MethodsThe 115 patients were mainly enrolled in the Inpatient Department of Dermatology, the First Affiliated Hospital, Zhengzhou University form March 1, 2013 to September 31, 2013, besides some of them were volunteers. We recorded the demographic characteristics, sun protection approches over the past five years, medical history, skin reflectance, tanning skin types, freckle features, hair colors, eye colors, and the clinico-dermoscopic features of acquired pigmented nevus in the 115 patients. Clinical and dermoscopic images of acquired pigmented nevus≥2mm in diameter were taken. Each acquired pigmented nevus were described, diagnosed, classified dermascopically by two experienced dermoscopists. Venous blood was drawed from each patient for genomic DNA extraction and sequiencing of the coding area of MC1 R gene, and the patient’s SNP loci and genotypes were identified. Statistics MC1 R gene SNP loci in coding area and genotypes. Finally Kruskal-Wallis test was applied to analyse the association between freckle features and skin reflectance, analyse the association between freckle features and the number of acquired pigmented nevus, analyse the association between MC1 R genotypes and skin reflectance, analyse the association between MC1 R genotypes and freckles, analyse the association between MC1 R genotypes and the number of acquired pigmented nevus, analyse the association between R163 Q genotypes and skin reflectance, analyse the association between R163 Q genotypes and freckles, analyse the association between R163 Q genotypes and the number of acquired pigmented nevus. Results1 Demography of the 115 patients: Gender frequency and distribution: 49(42.6%) male and 66(57.4%) female with a male to female was 1:0. 74. Age range: from 5.5 to 83 years old( mean ± standard deviation 38.19 ±16.62 years old). Ethnic group frequency and distribution: All the patients(100%) came from Chinese Han population. Ocupation frequency and distribution: 26(22.6%) farmers, 19(16.5%) unemployed people, 17(14.8%) staff, 16(13.9%) students, 15(13.0%) freelancers, laborers 13 cases(11.3%), 8(7.0%) medical workers, and 1(0.9%) teacher.2 Sun protection approaches taken by the patients: Over the past five years when they are going out never use sunglasses 106 cases(92.2%), wearing sunglasses 9 cases(7.8%) less than 50% of the time, no one is more than or equal to 50% of the time to wear sunglasses; Never wear a hat or open an umbrella 86 cases(74.8%), wear a hat or open an umbrella 21 cases(18.3%) less than 50% of the time, wear a hat or open an umbrella 8 cases(6.9%) more than or equal to 50% of the time; Never use sunscreen 94 cases(81.7%), use sunscreen 17 cases(14.8%) less than 50% of time, use sunscreen 4 cases(3.5%) more than or equal to 50% of the time; None has history of family melanoma and other skin cancer.3 Pigment phenotype of our patients: The rang of dorsal forearm skin reflectance: 19-99, the mean ± standard deviation was 45.3±12.8; the rang of volar forearm skin reflectance: 20-99, the mean ± standard deviation was 56.3±15.7; Skin type: Ⅲtype 47 cases(40.9%), Ⅳ type 68 cases(59.1%); Freckles: have freckles 20 cases(17.4%), no freckles 95cases(82.6%), which all located on the face, the color is light brown. Freckle score: 1 point: 95 cases(82.6%), 2 points: 12 cases(10.4%), 3 points: 6 cases(5.2%), 4 points: 2 cases(1.8%); Shoulder and hand Freckle score are 1 point: 115 cases(100%). Hair color: light: 5 cases(4.4%), dark brown: 49 cases(42.6%), black: 61 cases(53.0%); Eye color is brown.4 The clinical features of acquired pigmented nevus: In the 115 samples, the acquired pigmented nevus(< 2 mm), total 32 cases(27.8%), acquired pigmented nevus(≥2mm), total 83 cases(72.2%). The total number of acquired pigmented nevus(≥2mm) is 454. Color: pink 29(6.4%), light brown 79(17.4%), brown 189(41.6%), dark brown 144(31.7%), black 8(1.8%), blue 5(1.1%); Parts: head/neck 177(39.0%), trunk 169(37.2%), limbs 108(23.8%). Surface characteristics: plain 311(68.5%), raised 99(21.8%), dome 5(1.1%), papilloma 39(8.6%); Diameter range is 2 to 10 mm, the mean ± standard deviation is 4.3±2.1; Not have self-conscious symptom 82 cases(98.8%), feeling pruritus 1 case(1.2%), none feel pain. The total numbers of acquired pigmented nevus(≥5mm) are 52.5 The dermoscopic features of acquired pigmented nevus: reticular pattern : 106 cases(23.4%), globular pattern: 36 cases(7.9%), nonspecific pattern: 311 cases(68.5%), parallel furrow pattern: 1 case(0.2%); Signature pattern: nonspecific pattern: 62 cases(53.9%), nil pattern: 36 cases(31.3%), reticular pattern: 8 cases(7.0%), nonspecific globular pattern: 3 cases(2.6%), nonspecific reticular pattern: 3 cases(2.6%), globular pattern: 2 cases(1.7%), other pattern: 1 case(0.9%).6 There are four kinds of MC1 R genotypes in 98 Chinese Han population: r/r: 77 cases(78.6%), r/r/r: 7 cases(7.1%), r/r/r: 1 case(1.0%), r/wt: 13 cases(13.3%). 9 SNP: V92 M, S172 I, I120 T, R163 Q, T308 M, D184 N, R142 H, R223 W, R67 Q. Including R163Q-/- 42 cases(42.9%), R163 Q +/-and V92 M +/- 25 cases(25.5%), R163 Q +/- 8 cases(8.2%), R163 Q +/-and I120 T +/- 5 cases(5.1%), V92 M +/- 5 cases(5.1%), R67 Q +/-and R163Q-/- 3 cases(3.1%), V92M-/- 3 cases(3.1%), R163Q-/- and R223 W +/- 2 cases(2.0%), R142 H +/- and R163Q-/- 1 case(1.0%), R163Q-/- and D184 N +/- 1 case(1.0%), R163Q-/- and T308 M +/- 1 case(1.0%), I120 T +/- and V92M+/- 1 case(1.0%), S172I+/- V92 M +/- 1 case(1.0%).7 Kruskal-Wallis test was applied to analyse the association between freckle features and skin reflectance, analyse the association between freckle features and the number of acquired pigmented nevus, analyse the association between MC1 R genotypes and skin reflectance, analyse the association between MC1 R genotypes and freckles, analyse the association between MC1 R genotypes and the number of acquired pigmented nevus, analyse the association between R163 Q genotypes and skin reflectance, analyse the association between R163 Q genotypes and freckles, analyse the association between R163 Q genotypes and the number of acquired pigmented nevus. Finally the P respectively is: 0.418, 0.14, 0.787, 0.374, 0.184, 0.074, 0.188, 0.933, 0.869, 0.545, and 0.644. Conclusions1 AMNs in Chinese Han population are predominantly located on the head and face; their most common color is dark brown; and most of them are flat.2 The dermoscopic patterns of AMNs in Chinese Han population include reticular, globular, nonspecific, and parallel furrow pattern, with nonspecificas the most common pattern.3 There are four kinds of MC1 R genetypes in Chinese Han population, among which r/r is the most common one. There are 9 SNPs, and R163Q-/- is the most common SNP among them.4 There is no association between freckles and skin reflectance, mole count. There is no correlation of MC1 R genotypes and skin reflectance, freckles, mole count. There is no association of MC1 R polymorphism and clinico-dermoscopic features of acquired pigmented nevus.