Constitutive Skin Research Articles

Digital dermoscopy to determine skin melanin index as an objective indicator of skin pigmentation

<p class="Body">Clinical assessment of skin photosensitivity is subjectively determined by erythema and tanning responses to sunlight recalled by the subject, alternatively known as Fitzpatrick Skin Phototype (SPT). Responses may be unreliable due to recall bias, subjective bias by clinicians and subjects, and lack of cultural sensitivity of the questions. Analysis of red-green-blue (RGB) color spacing of digital images may provide an objective determination of SPT. This paper presents the studies to assess the melanin index (MI), as determined by RGB images obtained by both standard digital camera as well as by videodermoscope, and to correlate the MI with SPT based upon subjects’ verbal responses to standardized questions administered by a dermatologist.<br /> A sample of subjects representing all SPTs I–VI was selected. Both the digital camera and videodermoscope were calibrated at standard illumination, light source and white balance. Images of constitutive skin of the upper ventral arm were taken of each subject using both instruments.<strong> </strong>The studies showed that 58 subjects (20 M, 38 F) were enrolled in the study (mean age: 47 years; range: 20–89), stratified to skin phototype I–VI. MI obtained by using both digital camera and videodermoscope increased significantly as the SPT increased (<em>p</em> = 0.004 and <em>p</em> < 0.0001, respectively) and positively correlated with dermatologist-assessed SPT (Spearman correlation, <em>r</em> = 0.48 and <em>r</em> = 0.84, respectively).<strong> </strong>Digital imaging can quantify melanin content in order to quantitatively approximate skin pigmentation in all skin phototypes including Type VI skin. This methodology holds promise as a simple, non-invasive, rapid and objective approach to reliably determine skin phototype and, with further investigation, may prove to be both practical and useful in the prediction of skin cancer risk.</p>

Sun-Exposed Skin Color Is Associated with Changes in Serum 25-Hydroxyvitamin D in Racially/Ethnically Diverse Children

Background:UVB light from the sun increases serum 25-hydroxyvitamin D [25(OH)D] concentration, but this relation may depend on skin pigmentation among different racial/ethnic groups.Objective:We used quantitative measures of exposed (facultative) and unexposed (constitutive) skin color to examine relations between serum 25(OH)D concentration, tanning, race/ethnicity, and constitutive skin color over the summer, following winter vitamin D supplementation.Methods:The subjects (n = 426, mean age 11.7 ± 1.4 y, 51% female) were racially/ethnically diverse schoolchildren (57% non-white/Caucasian) enrolled in a 6-mo vitamin D supplementation trial (October–December to April–June). In this secondary analysis, measures of serum 25(OH)D concentration and skin color, with the use of reflectance colorimetry, were taken over a 6-mo period after supplementation, from pre-summer (April–June) to post-summer (September–December). Multiple linear regression was used to evaluate longitudinal relations.Results:Following supplementation, mean serum 25(OH)D concentration was 29.3 ± 9.5 ng/mL but fell to 25.6 ± 7.9 ng/mL (P < 0.0001) by the end of summer. The decrease in white/Caucasian children was less than in black/African American children (P < 0.01) and tended to be less than in Hispanic/Latino, Asian, and multiracial/other children (P = 0.19–0.50) despite similar changes in sun-exposed skin color among all groups. Tanning was significantly associated with post-summer serum 25(OH)D concentration (β = −0.15, P < 0.0001), as was race/ethnicity (P = 0.0002), but the later association disappeared after adjusting for constitutive skin color.Conclusions: Tanning significantly contributed to serum 25(OH)D concentration over the summer, independent of race/ethnicity, but was not sufficient to maintain serum 25(OH)D concentration attained with supplementation. Much of the variation in serum 25(OH)D concentration between racial/ethnic groups may be explained by skin color. This trial was registered at http://clinicaltrials.gov as NCT01537809.

Finger-shaped red light emitting diode to ascertain the depth of periungual wart

Management of periungual wart is a great challenge, especially when there is subungual extension. The major cause of recurrence of wart is improper clinical assessment of its extent and not directing therapy against the entire wart. This difficulty of ascertaining its extent could be overcome with this finger-shaped red light emitting diode device. Red light in the device penetrates the thick palmar skin and dark constitutive skin colour due to its longer wavelength.

Skin Pigmentation and Pigmentary Disorders: Focus on Epidermal/Dermal Cross-Talk.

Variation in human skin and hair color is the most notable aspect of human variability and several studies in evolution, genetics and developmental biology contributed to explain the mechanisms underlying human skin pigmentation, which is responsible for differences in skin color across the world's populations. Despite skin pigmentation is primarily related to melanocytes functionality, the surrounding keratinocytes and extracellular matrix proteins and fibroblasts in the underlying dermal compartment actively contribute to cutaneous homeostasis. Many autocrine/paracrine secreted factors and cell adhesion mechanisms involving both epidermal and dermal constituents determine constitutive skin pigmentation and, whenever deregulated, the occurrence of pigmentary disorders. In particular, an increased expression of such mediators and their specific receptors frequently lead to hyperpigmentary conditions, such as in melasma and in solar lentigo, whereas a defect in their expression/release is related to hypopigmented disorders, as seen in vitiligo. All these interactions underline the relevant role of pigmentation on human evolution and biology.

Evaluating the Photoprotective Effects of Ochre on Human Skin by In Vivo SPF Assessment: Implications for Human Evolution, Adaptation and Dispersal.

Archaeological indicators of cognitively modern behaviour become increasingly prevalent during the African Middle Stone Age (MSA). Although the exploitation of ochre is viewed as a key feature of the emergence of modern human behaviour, the uses to which ochre and ochre-based mixtures were put remain ambiguous. Here we present the results of an experimental study exploring the efficacy of ochre as a topical photoprotective compound. This is achieved through the in vivo calculation of the sun protection factor (SPF) values of ochre samples obtained from Ovahimba women (Kunene Region, Northern Namibia) and the Palaeozoic Bokkeveld Group deposits of the Cape Supergroup (Western Cape Province, South Africa). We employ visible spectroscopy, energy-dispersive X-ray fluorescence (ED-XRF), X-ray diffraction (XRD) and granulometric analyses to characterise ochre samples. The capacity of ochre to inhibit the susceptibility of humans to the harmful effects of exposure to ultraviolet radiation (UVR) is confirmed and the mechanisms implicated in the efficacy of ochre as a sunscreen identified. It is posited that the habitual application of ochre may have represented a crucial innovation for MSA humans by limiting the adverse effects of ultraviolet exposure. This may have facilitated the colonisation of geographic regions largely unfavourable to the constitutive skin colour of newly arriving populations.

Self‐reported skin colour and erythemal sensitivity vs. objectively measured constitutive skin colour in an African population with predominantly dark skin

Skin colour is an important factor in skin-related diseases. Accurate determination of skin colour is important for disease prevention and supporting healthy sun behaviour, yet such data are lacking for dark skin types. Self-perceived, natural skin colour and sun-skin reaction were compared with objectively measured skin colour among an African population with predominantly dark skin. Unexposed skin of 556 adults (70.1% Black) was measured with a reflectance spectrophotometer to calculate an individual typology angle (°ITA). Participants reported self-perceived skin colour and erythemal sensitivity. There was a strong, positive monotonic correlation between self-reported and measured skin colour (Spearman ρ=0.6438, P<0.001), but only a weak correlation between self-reported erythemal sensitivity and measured skin colour (Spearman ρ=0.2713, P<0.001). Self-report biases in underestimation and overestimation of skin colour were evident. Many participants with 'dark brown' and 'black' skin had difficulty in classifying erythemal sensitivity. In Africa, self-reported skin colour could potentially be used in lieu of spectrophotometer measurements, but options for questions on sunburn and tanning require suitable adjustment. Our study provides evidence of range in °ITA values among residents in Africa and reinforces previous results that self-report may be reliable for determining skin colour, but not erythemal sensitivity, for dark skin individuals.

Ultraviolet radiation after exposure to a low-fluence IPL home-use device: a randomized clinical trial.

The prevailing advice is to avoid sun exposure after intense pulsed light (IPL) hair removal. However, no systematic evaluation of ultraviolet radiation (UVR) after IPL hair removal exits. Therefore, we investigated the occurrence of side effects in subjects receiving solar-simulated UVR after a low-fluence IPL treatment with a home-use device. Sixteen subjects with Fitzpatrick skin types (FST) II-V were enrolled. Three constitutive buttock blocks (4.4 × 6.4 cm) were each subdivided into four sites, randomized to one IPL exposure of 0, 7, 8, or 10 J/cm2 (spectral output 530-1100 nm). Blocks were randomized to no UVR or three standard erythema doses (SEDs) UVR either 30 min or 24 h after IPL. Follow-up visits were 48 h, 1 week, and 4 weeks after IPL. Outcome measures were (i) clinical skin reactions, (ii) reflectance measurements of erythema and pigmentation, and (iii) pain. Subjects with FST II-IV experienced no skin reactions up to 4 weeks after IPL, neither erythema, edema, blisters, crusting, textual, nor pigment changes. Reflectance confirmed no change in erythema and pigmentation (p ≥ 0.090). UVR exposure induced erythema and increased pigmentation. The combination of IPL and UVR induced skin reactions not different to responses from UVR (IPL-UVR vs. UVR, p ≥ 0.164). Pain was generally low (median 1, range 0-4) and correlated positively with fluence and pigmentation (Spearman's rho ≥ 0.394, p < 0.001). One subject with FST V experienced perifollicular hyperpigmentation after IPL and slightly more intense when exposed to UVR. A single UVR exposure of three SEDs either shortly or 1 day after low-fluence IPL causes no amplification of skin responses in constitutive skin of individuals with FST II-IV.

A 3-Year Follow-up of Sun Behavior in Patients With Cutaneous Malignant Melanoma

IMPORTANCE UV radiation (UVR) exposure is the primary environmental risk factor for developing cutaneous malignant melanoma (CMM). OBJECTIVE To measure changes in sun behavior from the first until the third summer after the diagnosis of CMM using matched controls as a reference. DESIGN, SETTING, AND PARTICIPANTS Three-year follow-up, observational, case-control study performed from May 7 to September 22, 2009, April 17 to September 15, 2010, and May 6 to July 31, 2011, at a university hospital in Denmark of 21 patients with CMM and 21 controls matched to patients by sex, age, occupation, and constitutive skin type participated in the study. Exposure to UVR was assessed the first and second summers (n=20) and the first and third summers (n=22) after diagnosis. Data from 40 participants were analyzed. MAIN OUTCOMES AND MEASURES Exposure to UVR was assessed by personal electronic UVR dosimeters that measured time-related UVR in standard erythema dose (SED) and corresponding sun diaries (mean, 74 days per participant each participation year). RESULTS Patients' daily UVR dose and UVR dose in connection with various behaviors increased during follow-up (quantified as an increase in daily UVR dose each year; all days: mean, 0.3 SED; 95% CI, 0.05-0.5 SED; days with body exposure: mean, 0.6 SED; 95% CI, 0.07-1.2 SED; holidays: mean, 1.2 SED; 95% CI, 0.3-2.1 SED; days abroad: 1.9 SED; 95% CI, 0.4-3.4 SED; and holidays with body exposure: mean, 2.3 SED; 95% CI, 1.1-3.4 SED). After the second year of follow-up, patients' UVR dose was higher than that of controls, who maintained a stable UVR dose. No difference was found between groups in the number of days with body exposure or the number of days using sunscreen in the second and third years of follow-up. CONCLUSIONS AND RELEVANCE Our findings suggest that patients with CMM do not maintain a cautious sun behavior in connection with an increase in UVR exposure, especially on days with body exposure, when abroad, and on holidays.

Association of serum 25-hydroxyvitamin D with race/ethnicity and constitutive skin color in urban schoolchildren.

The objective of this study was to determine the extent to which constitutive skin color explains racial/ethnic differences in serum 25-hydroxyvitamin D (25OHD) concentrations in urban schoolchildren. Analysis of covariance (ANCOVA) was used to determine associations of 25OHD with parent-reported race/ethnicity and constitutive skin color as measured by reflectance colorimeter [individual typology angle (ITA°; higher value corresponds to lighter skin)] in 307 Greater Boston schoolchildren aged 9-15 during October-December 2011. Nearly 60% of all children were inadequate in 25OHD (<20 ng/mL). Prevalence of inadequate 25OHD differed by race/ethnicity (p<0.001): white (46.6%), black (74.5%), Hispanic (64.7%), Asian (88.9%), and multi-racial/other (52.7%). Serum 25OHD increased 0.6 ng/mL per 10° increase in ITA° value (p<0.001). The prediction of 25OHD by race/ethnicity was slightly stronger than the prediction by skin color in separate models (R2=0.19, R2=0.16, respectively). Most of the variability in 25OHD in race/ethnicity was due to constitutive skin color in this group of racially diverse US children.

The role of natural and UV‐induced skin pigmentation on low‐fluence IPL‐induced side effects: A randomized controlled trial

The risk of adverse skin effects following light-based hair removal is greater in pigmented skin based on the theory of selective photothermolysis. Thus sunlight-induced pigment i.e., facultative pigmentation, increases the risk of adverse skin effects, perhaps disproportionately. The aim of this study was to evaluate the influence of constitutive and facultative skin pigmentation on low-fluence intense pulsed light (IPL)-induced adverse skin effects. Twenty-one subjects with Fitzpatrick skin type II-IV were enrolled. Two buttock blocks were randomized to receive 0 or 8 solar simulated ultraviolet radiation (UVR) exposures of consecutively increasing Standard Erythema Doses (2-4 SED). Each block was subdivided into four sites, randomized to receive IPL of 0, 7, 8, or 10 J/cm(2) , once a week for 3 weeks. Biopsies were taken 16-24 hours after the first IPL exposure and subjects were seen 1 and 4 weeks after the last IPL exposure. Outcome measures were: (i) skin reactions, (ii) pain, (iii) mRNA expression of pigment-markers microphthalmia-associated transcription factor (MITF) and pro-opiomelanocortin (POMC), and (iv) clinical appearance of biopsy wounds. Skin pigmentation increased after UVR (baseline median 13.8%, after UVR 28.1%, P = 0.0001) in all skin types. Subjects reported low pain intensities (median 1.5, scale 0-10) and experienced transient erythema immediately after IPL exposure. No persistent erythema, blisters, crusting, textual, or pigment changes were observed. The risk of erythema and pain intensities increased with IPL dose and skin pigmentation (P < 0.03). There was no difference in pain or skin reactions in skin with similar degree of natural and facultative pigmentation (P ≥ 0.104). Expression of cellular pigment-markers was not influenced by IPL exposure, neither in constitutive nor in facultative pigmented skin. Clinical appearance of biopsy wounds was unaffected by IPL exposure. The prevalence and intensity of low-fluence IPL-induced adverse skin effects depended on IPL dose and skin pigmentation regardless of the origin, i.e., constitutive versus UV induced.

Is increased constitutive skin and hair pigmentation an early sign of puberty?

The paper analyzes data concerning the constitutive skin and hair pigmentation of 7–10-year-old Polish children to examine whether the hormonal activity of the gonads, which increases in this period, causes changes in pigmentation levels that may be considered an early sign of puberty. The study involved 289 children (151 girls and 138 boys). Skin pigmentation was examined on the medial side of the arm, while hair pigmentation on strands of hair close to the scalp in the occipital area. Additionally, body height (B-v) was measured and compared with population norms. On this basis, it was ascertained that the studied sample was representative of the population from which it was taken and that it represented the prepubertal and early pubertal stages of ontogeny (prior to the pubertal growth spurt or the first menstruation in the studied girls). It was found that in 7–10-year-old Polish children there is a statistically significant (p=0.001) increase in skin and hair pigmentation levels, while the degree of pigmentation of both structures at this stage of ontogeny is sexually dimorphic: girls are characterized by stronger pigmentation than boys. At the age of 10 years, the dimorphic differences in skin pigmentation intensify due to a rapid rise in pigmentation in girls. This change may be deemed an early morphological sign of puberty, as it precedes the pubertal growth spurt and menarche. This fast increase in skin pigmentation is not paralleled by an analogous change in hair pigmentation.

Constitutive and Relative Facultative Skin Pigmentation among Victorian Children Including Comparison of Two Visual Skin Charts for Determining Constitutive Melanin Density

Our aim was to examine the association between ethnicity, phenotype, sun behavior and other characteristics, and constitutive and relative facultative skin pigmentation. A total of 191 participants were recruited, with a mean age of 7.6 years (SD 3.4), during 2009-2011 from Maternal and Child Health Centres (MCHC) and schools in Melbourne, Australia. Parental questionnaire data were obtained on sun behavior and examination consisted of noting the child's natural skin, hair and eye color, ethnicity, nevi count and spectrophotometric melanin density (MD). Constitutive skin pigmentation was estimated from buttock MD. Relative facultative skin pigmentation was estimated by hand compared with buttock absorption. Ethnicity, hair color and skin color were associated with constitutive and facultative skin pigmentation on univariate analysis. Higher ambient ultraviolet radiation (UVR) in the past month, greater freckling, greater nevi and increased sun exposure over the past year were related to darker facultative skin pigmentation. Sun exposure over the life course was not. The two skin charts accounted for 39.7% and 21.4% of buttock MD, respectively. Relative facultative skin pigmentation is associated with recent UVR levels, not life-course sun exposure. Relative facultative skin pigmentation may not be a useful measure of sun exposure over the early life course. Skin color charts can be used to assess constitutive skin pigmentation if spectrophotometry is not available.

Sun behaviour after cutaneous malignant melanoma: a study based on ultraviolet radiation measurements and sun diary data

It has been reported that patients with cutaneous malignant melanoma (CMM) can lower their risk of a second primary melanoma by limiting recreational sun exposure. Previous studies based on questionnaires and objective surrogate measurements indicate that before their diagnosis, patients with CMM are exposed to higher ultraviolet radiation (UVR) doses than controls, followed by a reduction after diagnosis. In a prospective, observational case-control study, we aimed to assess sun exposure after diagnosis of CMM by objective measurements to substantiate advice about sun behaviour. The study population consisted of 24 patients recently diagnosed with CMM during the 7 months preceding the start of the study; 51 controls who matched these recently diagnosed patients in age, sex, occupation and constitutive skin type; and 29 patients diagnosed with CMM between 12 months and 6 years before the start of the study. During a summer season participants filled in sun exposure diaries daily and wore personal electronic UVR dosimeters in a wristwatch that continuously measured time-stamped UVR doses in standard erythema dose. The UVR dose of recently diagnosed patients on days with body exposure was one-third lower, and the number of days using sunscreen was double that of matched controls. However, in patients diagnosed more than 12 months earlier, the UVR dose on days with body exposure was one-third higher and the number of days using sunscreen was half that of recently diagnosed patients. Patients with CMM limited their UVR dose on days with body exposure, and by using sunscreen further reduced UVR reaching the skin, although only immediately after diagnosis.

Assessing skin pigmentation in epidemiological studies: The reliability of measurements under different conditions

Different devices are used for the non-invasive measurement of (constitutive) skin pigmentation in (epidemiological) studies. Reproducibility of measurements with the Chromameter (CM, model CR 300, Minolta, Osaka) and the Reflectometer (RM, Courage & Khazaka, Cologne) has not yet been examined in detail and was addressed in a set of four experiments and studies respectively. Regarding the CM, the Y value of the Yxy CIE 1931 colour system was utilized, representing lightness in this colour space, while the RM measured reflectance at 660nm with a small bandwidth of 20nm. Both devices measure reflectance on a scale from 0 to 100%, however, in different wavelength ranges. Between 3 and 20 repetitions were performed on standard grey scales and different sets of human volunteers, including RM measurements in a large epidemiological field study. While the coefficient of variation (V) increases and the intraclass correlation coefficient decreases from controlled laboratory to field conditions, reproducibility remained in a range considered acceptable, if adequate study conditions were maintained. In a direct comparison on human skin, V of the RM was significantly smaller than that of the CM. Both devices can be used confidently in field studies; however, based on considerations of skin optics and in view of slightly lesser variability, the RM may be preferable.

Immune evasion or avoidance: Fungal skin infection linked to reduced defence peptides in Australian green-eyed treefrogs, Litoria serrata

Many parasites and pathogens suppress host immunity to maintain infection or initiate disease. On the skin of many amphibians, defensive peptides are active against the fungus Batrachochytrium dendrobatidis (Bd), the causative agent of the emerging infectious disease chytridiomycosis. We tested the hypothesis that infection with the fungus may be linked to lower levels of defensive peptides. We sampled both ambient (or constitutive) skin peptides on the ventral surface immediately upon capture, and stored skin peptides induced from granular glands by norepinephrine administration of Australian green-eyed treefrogs, Litoria serrata. Upon capture, uninfected frogs expressed an array of antimicrobial peptides on their ventral surface, whereas infected frogs had reduced skin peptide expression. Expression of ambient skin peptides differed with infection status, and antimicrobial peptides maculatin 1.1 and 2.1 were on average three times lower on infected frogs. However, the repertoire of skin peptides stored in granular glands did not differ with infection status; on average equal quantities were recovered from infected and from uninfected frogs. Our results could have at least two causes: (1) frogs with reduced peptide expression are more likely to become infected; (2) Bd infection interferes with defence peptides by inhibiting release or causing selective degradation of peptides on the skin surface. Immune evasion therefore may contribute to the pathogenesis of chytridiomycosis and a mechanistic understanding of this fungal strategy may lead to improved methods of disease control.

Essential Role of RAB27A in Determining Constitutive Human Skin Color

Human skin color is predominantly determined by melanin produced in melanosomes within melanocytes and subsequently distributed to keratinocytes. There are many studies that have proposed mechanisms underlying ethnic skin color variations, whereas the processes involved from melanin synthesis in melanocytes to the transfer of melanosomes to keratinocytes are common among humans. Apart from the activities in the melanogenic rate-limiting enzyme, tyrosinase, in melanocytes and the amounts and distribution patterns of melanosomes in keratinocytes, the abilities of the actin-associated factors in charge of melanosome transport within melanocytes also regulate pigmentation. Mutations in genes encoding melanosome transport-related molecules, such as MYO5A, RAB27A and SLAC-2A, have been reported to cause a human pigmentary disease known as Griscelli syndrome, which is associated with diluted skin and hair color. Thus we hypothesized that process might play a role in modulating skin color variations. To address that hypothesis, the correlations of expression of RAB27A and its specific effector, SLAC2-A, to melanogenic ability were evaluated in comparison with tyrosinase, using human melanocytes derived from 19 individuals of varying skin types. Following the finding of the highest correlation in RAB27A expression to the melanogenic ability, darkly-pigmented melanocytes with significantly higher RAB27A expression were found to transfer significantly more melanosomes to keratinocytes than lightly-pigmented melanocytes in co-culture and in human skin substitutes (HSSs) in vivo, resulting in darker skin color in concert with the difference observed in African-descent and Caucasian skins. Additionally, RAB27A knockdown by a lentivirus-derived shRNA in melanocytes concomitantly demonstrated a significantly reduced number of transferred melanosomes to keratinocytes in co-culture and a significantly diminished epidermal melanin content skin color intensity (ΔL* = 4.4) in the HSSs. These data reveal the intrinsically essential role of RAB27A in human ethnic skin color determination and provide new insights for the fundamental understanding of regulatory mechanisms underlying skin pigmentation.

Spontaneous Skin Erosions and Reduced Skin and Corneal Wound Healing Characterize CLIC4NULL Mice

Cutaneous wound healing is a complex process involving blood clotting, inflammation, migration of keratinocytes, angiogenesis, and, ultimately, tissue remodeling and wound closure. Many of these processes involve transforming growth factor-β (TGF-β) signaling, and mice lacking components of the TGF-β signaling pathway are defective in wound healing. We show herein that CLIC4, an integral component of the TGF-β pathway, is highly up-regulated in skin wounds. We genetically deleted murine CLIC4 and generated a colony on a C57Bl/6 background. CLIC4(NULL) mice were viable and fertile but had smaller litters than did wild-type mice. After 6 months of age, up to 40% of null mice developed spontaneous skin erosions. Reepithelialization of induced full-thickness skin wounds and superficial corneal wounds was delayed in CLIC4(NULL) mice, resolution of inflammation was delayed, and expression of β4 integrin and p21 was reduced in lysates of constitutive and wounded CLIC4(NULL) skin. The induced level of phosphorylated Smad2 in response to TGF-β was reduced in cultured CLIC4(NULL) keratinocytes relative to in wild-type cells, and CLIC4(NULL) keratinocytes migrated slower than did wild-type keratinocytes and did not increase migration in response to TGF-β. CLIC4(NULL) keratinocytes were also less adherent on plates coated with matrix secreted by wild-type keratinocytes. These results indicate that CLIC4 participates in skin healing and corneal wound reepithelialization through enhancement of epithelial migration by a mechanism that may involve a compromised TGF-β pathway.

Gene mapping study for constitutive skin color in an isolated Mongolian population

To elucidate the genes responsible for constitutive human skin color, we measured the extent of skin pigmentation in the buttock, representative of lifelong non-sun-exposed skin, and conducted a gene mapping study on skin color in an isolated Mongolian population composed of 344 individuals from 59 families who lived in Dashbalbar, Mongolia. The heritability of constitutive skin color was 0.82, indicating significant genetic association on this trait. Through the linkage analysis using 1,039 short tandem repeat (STR) microsatellite markers, we identified a novel genomic region regulating constitutive skin color on 11q24.2 with an logarithm of odds (LOD) score of 3.39. In addition, we also found other candidate regions on 17q23.2, 6q25.1, and 13q33.2 (LOD ≥ 2). Family-based association tests on these regions with suggestive linkage peaks revealed ten and two significant single nucleotide polymorphisms (SNPs) on the linkage regions of chromosome 11 and 17, respectively. We were able to discover four possible candidate genes that would be implicated to regulate human skin color: ETS1, UBASH3B, ASAM, and CLTC.

Linkage and association scan for tanning ability in an isolated Mongolian population

Tanning ability is important, because it represents the ability of the skin to protect itself against ultraviolet (UV) radiation. Here, we sought to determine genetic regions associated with tanning ability. Skin pigmentation was measured at the outer forearm and buttock areas to represent facultative and constitutive skin color, respectively. In our study population consisting of isolated Mongolian subjects, with common histories of environmental UV exposure during their nomadic life, facultative skin color adjusted by constitutive skin color was used to indicate tanning ability. Through linkage analysis and family-based association tests of 345 Mongolian subjects, we identified 2 potential linkage regions regulating tanning ability on 5q35.3 and 12q13.2, having 6 and 7 significant single nucleotide polymorphisms (SNPs), respectively. Those significant SNPs were located in or adjacent to potential candidate genes related to tanning ability: GRM6, ATF1, WNT1, and SILV/Pmel17.

Genetic variants and skin colour in Danes

In this study, 33 single nucleotide polymorphisms (SNPs) in known pigmentation genes were tested for association to objective spectrophotometric reflectance measurements of the upper-inner arm and the buttock in 188 unrelated Danes. The 188 Danes were typed for 33 SNPs by two multiplex PCRs, two multiplex single base extension reactions and capillary electrophoresis. To further investigate the role of the SNPs, their allelic distribution was compared to those in a population of 36 Somalis. Four MC1R SNP alleles (R151C, R160W, D294H and 29insA) showed significant associations to light skin pigmentation in individuals who were either homozygous or compound heterozygous. This confirms the regulatory role of MC1R in skin pigmentation. SNP loci in SLC45A2, SLC24A5 and TYR showed large allele frequency differences between Somalis and Danes, which suggested a possible role in skin pigmentation. The average buttock pigmentation was significantly lighter than the average upper-inner arm pigmentation. Therefore, the buttock reflectance measurements better resemble the constitutive skin colour compared to upper-inner arm reflectance measurements and will be used in future studies.