Dark-skinned Populations Research Articles

Apoptosis Pathway-Associated Proteins Are Frequently Expressed in Melanoma: A Study of 32 Cases With Focus on Acral Lentiginous Melanoma.

Acral lentiginous melanoma (ALM) is an aggressive type of cutaneous melanoma (CM) that arises on palms, soles, and nail units. ALM is rare in White population, but it is relatively more frequent in dark-skinned populations. There is an unmet need to develop new personalized and more effective treatments strategies for ALM. Increased expression of antiapoptotic proteins (ie, BCL2, MCL1) has been shown to contribute to tumorigenesis and therapeutic resistance in multiple tumor types and has been observed in a subset of ALM and mucosal melanoma cell lines in vivo and in vitro. However, little is known about their expression and clinical significance in patients with ALM. Thus, we assessed protein expression of BCL2, MCL1, BIM, and BRAF V600E by immunohistochemistry in 32 melanoma samples from White and Hispanic populations, including ALM and non-ALM (NALM). BCL2, MCL1, and BIM were expressed in both ALM and NALM tumors, and no significant differences in expression of any of these proteins were detected between the groups, in our relatively small cohort. There were no significant associations between protein expression and BRAF V600E status, overall survival, or ethnicity. In summary, ALM and NALM demonstrate frequent expressions of apoptosis-related proteins BCL2, MCL1, and BIM. Our findings suggest that patients with melanoma, including ALM, may be potential candidates for apoptosis-directed therapies.

Real-world data of 5-aminolaevulinic acid-mediated photodynamic therapy for Bowen disease: a 10-year retrospective study in patients with darker-coloured skin (2011-2021).

Photodynamic therapy (PDT) has been strongly recommended as an excellent alternative treatment for Bowen disease (BD). However, reported data on 5-aminolaevulinic acid-mediated PDT (ALA-PDT) with red-light irradiation are limited and the long-term effectiveness remains to be determined, especially in dark-skinned populations. We aimed to review routine clinical practice in the field of BD treatment with ALA-PDT over an extended study period (2011-2021), calculate the overall clearance rate, and explore and evaluate factors that might affect the effectiveness of therapy in a real-world setting. The medical records of patients with BD who received ALA-PDT with red-light irradiation between February 2011 and June 2021 were reviewed and summarized. Univariate and multivariate analyses of clinically relevant variables that may affect treatment outcomes were conducted to identify risk predictors. The overall clearance rate of 122 BD lesions was 89.3% with a median follow-up time of 36 months. The correlation between the effectiveness and fluorescence intensity of pre-PDT or PDT sessions was statistically significant after eliminating the interference of confounding factors. All recurrences occurred in the first 2 years following ALA-PDT. ALA-PDT is an effective treatment for BD in patients with darker-coloured skin. Well-executed operations and effective pretreatment are the determinants of effectiveness. Fluorescence intensity of pre-PDT appeared to be a significant predictor of final effectiveness. In addition, 2 years of follow-up is necessary following ALA-PDT.

Basal Cell Carcinoma: Diagnosis, Management and Prevention

Basal cell carcinoma (BCC) is a slow-growing, locally aggressive, rarely metastasizing, low-grade cutaneous neoplasm that arises from the epidermal basal layer and invades the adjoining tissues. It is the most common skin cancer. It is fairly common in fair Caucasians and quite uncommon in dark-skinned populations. It contributes to 65–75% of cutaneous malignancies in whites and 20–30% in Asian Indians. The most important causal factors appear to be radiation exposure and genetic predisposition. It may present as a nonhealing lesion that occasionally bleeds or as a pruritic lesion with no symptoms. Tumours rarely spread to regional lymph nodes. The clinical appearances and morphology of BCC are diverse. Clinical types include nodular, cystic, superficial, pigmented, morphoeaform, (sclerosing), keratotic and fibroepithelioma of Pinkus. Most of the lesions appear on the head and neck, usually above the line joining the tragus and the angle of the mouth. A biopsy should be performed on all lesions suspected of BCC. The primary aim of treatment is the complete excision of the tumour tissue. Other treatment modalities include cryotherapy, immunomodulatory drugs, laser treatment or locally applicable chemotherapeutic agents. Prevention consists of lifestyle changes such as avoiding sunburn, tanning beds and prolonged direct sun exposure, shade seeking, sunscreen application on the skin, and physical barrier methods such as protective clothing, hats and sunglasses. Regular sunscreen use in childhood and adolescence seems more beneficial than in adulthood.

Hyperpigmented Mycosis Fungoides Masquerading as Longstanding Lichen Planus Pigmentosus: A Diagnostic Pitfall.

Mycosis fungoides (MF) is a rare primary cutaneous T-cell lymphoma, accounting for 50%-60% of all cutaneous T-cell lymphoma cases. It has a prevalence of approximately 5-6 cases per 1 million people annually and a higher incidence in dark-skinned populations. We report a case of hyperpigmented MF in a 72-year-old dark-skinned man with a 5-year history of progressive, widespread poikilodermatous patches and thin plaques on the back and bilateral legs. The patient had been treated for lichen planus pigmentosus for 5 years without significant response to therapy. Multiple biopsies revealed a band-like lymphoid infiltrate in the dermis, accompanied by intraepidermal lymphocytes, some of which had larger hyperchromatic nuclei. CD4 + T lymphocytes were predominant over CD8 + T-positive cells located along the epidermis, dermoepidermal junction, and in the dermis. A diagnosis of hyperpigmented MF was made based on the clinical, histopathological, and immunohistochemical findings. This case report highlights the importance of considering hyperpigmented MF as a differential diagnosis in patients with longstanding lichen planus pigmentosus, particularly when there is a lack of response to therapy.

Favre-Racouchot syndrome and chronic obstructive pulmonary disease – a common link

Introduction and aim. Favre-Racouchot syndrome though mostly reported in Caucasian men (with an estimated prevalence of 6% in adults older than 50 years), cases have been reported in dark-skinned population including Indians, albeit rarely. It is characterized by large open and closed comedones along with epidermal cysts over the nose, cheeks, temples, forehead and periorbital areas. The association of this condition with chronic heavy smoking is what it makes compelling. Description of the case report. We report a case of elderly male, chronic heavy smoker who was diagnosed as a case of chronic obstructive pulmonary disease (COPD) as per standard guidelines. He presented with multiple nodulo-cystic lesions and had undergone a skin biopsy. Histomorphology features were consistent with Favre-Racouchot syndrome. Conclusion. Early identification of this skin condition in mildly symptomatic and asymptomatic smokers may help clinicians to forewarn the patients regarding development of chronic obstructive pulmonary disease (COPD).

Individual participant data (IPD)-level meta-analysis of randomised controlled trials to estimate the vitamin D dietary requirements in dark-skinned individuals resident at high latitude.

There is an urgent need to develop vitamin D dietary recommendations for dark-skinned populations resident at high latitude. Using data from randomised controlled trials (RCTs) with vitamin D3-supplements/fortified foods, we undertook an individual participant data-level meta-regression (IPD) analysis of the response of wintertime serum 25-hydroxyvitamin (25(OH)D) to total vitamin D intake among dark-skinned children and adults residing at ≥ 40° N and derived dietary requirement values for vitamin D. IPD analysis using data from 677 dark-skinned participants (of Black or South Asian descent; ages 5-86years) in 10 RCTs with vitamin D supplements/fortified foods identified via a systematic review and predefined eligibility criteria. Outcome measures were vitamin D intakeestimates across a range of 25(OH)D thresholds. To maintain serum 25(OH)D concentrations ≥ 25 and 30nmol/L in 97.5% of individuals, 23.9 and 27.3µg/day of vitamin D, respectively, were required among South Asian and 24.1 and 33.2µg/day, respectively, among Black participants. Overall, our age-stratified intake estimates did not exceed age-specific Tolerable Upper Intake Levels for vitamin D. The vitamin D intake required by dark-skinned individuals to maintain 97.5% of winter 25(OH)D concentrations ≥ 50nmol/L was 66.8µg/day. This intake predicted that the upper 2.5% of individuals could potentially achieve serum 25(OH)D concentrations ≥ 158nmol/L, which has been linked to potential adverse effects in older adults in supplementation studies. Our IPD-derived vitamin D intakes required to maintain 97.5% of winter 25(OH)D concentrations ≥ 25, 30 and 50nmol/L are substantially higher than the equivalent estimates for White individuals. These requirement estimates are also higher than those currently recommended internationally by several agencies, which are based predominantly on data from Whites and derived from standard meta-regression based on aggregate data. Much more work is needed in dark-skinned populations both in the dose-response relationship and risk characterisation for health outcomes. PROSPERO International Prospective Register of Systematic Reviews (Registration Number: CRD42018097260).

Clinical and histological characteristics, and management of melanoma in French Guiana, 2007-2018.

There are few studies available on melanoma in Afro‐Caribbean and Amerindian populations of South America. French Guiana deserves a study due to its specific health system and diversity of phototypes. The objectives of this study were to evaluate the incidence, histological and clinical characteristics of melanoma in French Guiana. A retrospective study was conducted from October 2007 to January 2018 on all primary melanomas observed at the Cayenne Hospital Centre. Thirty‐nine patients were included. The incidence rate (1.61/106 inhabitants/year) was low compared with mainland France. Median age was 58, and gender ratio 1 : 16. Clear phototype (I/II) patients were the most frequent (38.5%), but a significant amount of melanoma also occurred in darker skin. Median Breslow was higher in dark phototypes than in fair‐skinned patients. Superficial spreading melanoma (SSM) was the most common histological type (33.3%), particularly in patients with clear phototype (61.5%). Acral lentiginous melanoma was found only in darker‐skinned patients (29.1%). The trunk was involved in 66.6% in the clearest group whereas foot was the most common location in the darkest group (60% in V/VI phototypes). Surgery was the most frequently used treatment (79.5%). At the end of the study period, 53.8% had been lost to follow‐up. In conclusion, the incidence of melanoma in French Guiana is lower than in mainland France but remains a public health concern, as dark‐skinned populations often present with advanced diseases. Awareness and prevention in these communities must be improved.

Childhood longitudinal melanonychia: case series from Poland.

IntroductionLongitudinal melanonychia (LM) is characterized by a tan, brown or black longitudinal streak within nail plate caused by the presence of melanin. LM is relatively common in dark-skinned population, infrequent in Caucasian population, and rare in children.AimWe report epidemiological, clinicopathological and dermoscopic analysis of 8 cases of childhood LM from Poland, which is the largest series in the Central and Eastern European population.Material and methodsThree hundred and forty-eight patients presenting with various nail pigmentation (in 2010–2016) were analysed. 72 cases of LM have been identified, including 8 cases of childhood LM (< 16 years of age), which were included in further analysis.ResultsSeven patients were boys and one girl, with mean age of 9 years (range: 6–13). More than a half (n = 5) presented skin phototype II. The most common location of melanonychia was the first left fingernail. Dermoscopy revealed heterogeneity of longitudinal lines colour in 5 cases. The irregularity of longitudinal line thickness in 5 cases and irregularity of parallelism in 5 cases was observed. Histopathological evaluation was performed in 4 patients, in 3 cases it revealed the presence of nail matrix nevus, in one case the presence of melanocytic proliferation of the lentiginous pattern along the dermoepidermal junction.ConclusionsDespite the fact that melanoma was not recognised in any case, such a possibility should always be considered as the cause of LM, even in the paediatric population. Dermoscopy seems to be useful in patient follow-up and management.

Individual participant data (IPD)-level meta-analysis of randomised controlled trials among dark-skinned populations to estimate the dietary requirement for vitamin D

BackgroundEstimation of the dietary requirements for vitamin D is crucial from a public health perspective in providing a framework for the prevention of vitamin D deficiency. It has been shown that pooling individual participant-level data (IPD) from selected randomised controlled trials (RCTs) of white children and adults facilitated the generation of more accurate estimates of the vitamin D requirement. Recent RCT data suggest the vitamin D requirement of dark-skinned, particularly black, individuals, an at-risk group of vitamin D deficiency, is greater than those of white counterparts. Thus, we wished to develop a study protocol for the conduct of an IPD-level meta-analysis of vitamin D requirements using data from appropriate vitamin D RCTs in dark-skinned population subgroups.MethodsThe study protocol details the steps needed within such an IPD meta-analysis which will include its registration, constituent systematic review to identify all appropriate RCTs on the basis of pre-specified eligibility criteria, the associated data collection, handling, and synthesis, as well as checking the integrity of the IPD, followed by implementation of a one/two-stage IPD meta-analysis and derivation of vitamin D requirement estimates.DiscussionAs dark-skinned population subgroups are at increased risk of vitamin D deficiency, further investigation of dietary recommendations for vitamin D in these subgroups is needed. We strongly believe that application of an IPD-based meta-analysis is a highly strategic approach by which to undertake some of this further investigation. Such IPD-based analysis, however, will need collaboration across the principal investigators of the identified RCTs meeting with the eligibility criteria, and the availability of this study protocol will be important to highlight the potential of IPD-based analysis for estimation of the dietary requirement for vitamin D for this particular population subgroup as well as for other at-risk target populations.Systematic review registrationPROSPERO International Prospective Register of Systematic Reviews (registration number: CRD42018092343).

Modification of the Fitzpatrick system of skin phototype classification for the Indian population, and its correlation with narrowband diffuse reflectance spectrophotometry.

The Fitzpatrick classification for skin phototyping is widely used, but its usefulness in dark-skinned populations has been questioned by some researchers. Recently, skin colour measurement has been proposed for phototyping skin colour objectively. To modify the Fitzpatrick system of skin phototyping for the Indian population and to study its correlation with skin colour using narrowband diffuse reflectance spectrophotometry METHODS: Answer choices for three items (eye colour, hair colour, colour of unexposed skin) out of 10 in the original Fitzpatrick questionnaire were modified, followed by self-administration of the original and the modified Fitzpatrick questionnaire by 70 healthy Indian volunteers. Skin colour (melanin and erythema indices) was measured from two photoexposed and two photoprotected sites using a narrowband reflectance spectrophotometer. The mean ± SD scores for the original and modified Fitzpatrick questionnaires were 25.40 ± 4.49 and 23.89 ± 4.82, respectively (r = 0.97, P < 0.001). The two items related to tanning habits were deemed irrelevant based on the subjects' response and were removed from the modified questionnaire. The Melanin Index (MI) of all sites correlated moderately well with both the modified (r = 0.61-0.64, P < 0.001) and original Fitzpatrick questionnaire scores (r = 0.64-0.67, P < 0.001), while the Erythema Index showed poor correlation with both. An MI value of ≧42 was found to be the cut-off between skin phototypes I-III and IV, and ≥ 47 between IV and V-VI. Our modification of the Fitzpatrick questionnaire makes it more relevant to the Indian population. Spectrophotometry can be a useful objective tool for skin phototyping.

Dermoscopy and patch testing in patients with lichen planus pigmentosus on face: A cross-sectional observational study in fifty Indian patients.

Lichen planus pigmentosus (LPP) is a common cause of facial melanosis in the dark-skinned population. At present, information on dermoscopy and patch testing in LPP is limited. To describe dermoscopic findings and study the role of patch testing in patients with LPP on the face. Facial lesions of 50 patients with LPP were studied dermoscopically, followed by histological evaluation. Patch and photopatch tests with the Indian Standard Series and Scandinavian series, respectively, and patient's own cosmetics were performed on all patients. The most common dermoscopic finding was dots and/or globules (43/50, 86%) in different patterns: hem-like (20.9%), arcuate (18.6%), incomplete reticular (39.5%), complete reticular (7%), and not otherwise specified (14%). Other patterns were exaggerated pseudoreticular pattern, accentuation of pigmentation around follicular openings, targetoid appearance, and obliteration of the pigmentary network. There were 26 relevant patch tests in 17 (34%) patients: para-phenylenediamine (n = 5), nickel (n = 3), colophony, perfume mix and fragrance mix (n = 2 each), thiuram mix and 3,3,4,5-tetrachlorosalicylanilide (n = 1 each), and patients' own products (n = 9). The only positive photopatch test was to fentichlor. No clinical or histological finding differed significantly based on patch test results. The only dermoscopic finding to be statistically associated with a positive patch test was the non-characteristic arrangement of dots/globules (P = 0.042). Dermoscopic features were not correlated with clinical features or disease duration. Implications of patch testing on the management of LPP cannot be commented upon as ours was a cross-sectional study. The present study describes the dermoscopic findings of facial lesions in LPP. Our patch test results suggest a probable role of allergens in causing LPP on the face.

Study of efficacy of phototherapy (psoralen with ultraviolet A and narrow-band ultraviolet B) in vitiligo

Background: Vitiligo is the most common depigmenting disorder. It is more significant in the dark-skinned population, with a major impact on the quality of life of patients. Phototherapy has been the mainstay of treatment for a long time. Both psoralens with ultraviolet A (PUVA) and narrow-band ultraviolet B (NB-UVB) therapy have shown satisfactory results. Aims: To study the efficacy of phototherapy (PUVA and NB-UVB) in patients with vitiligo and to compare the response to phototherapy (PUVA vs. NB-UVB) in vitiligo. Methods: This is a prospective study of 60 patients recruited from the patients attending the dermatology outpatient department of KEM Hospital, Pune. Thirty patients each were randomly allotted to either PUVA or NB-UVB group. Therapy was given thrice a week for PUVA and twice a week for NB-UVB on nonconsecutive days. Patients were followed-up every month for 1 year. Two primary parameters, repigmentation and arrest of progression of disease activity, were considered. Results: Our study showed that both PUVA and NB-UVB are effective in the treatment of vitiligo. Both treatment methods showed a good repigmentation especially over the face, with a poor response on the feet and hands. The overall grade of repigmentation was better with NB-UVB than PUVA. The adverse effects were marginally more with PUVA therapy. Conclusion: Thus, it was proven in our study that both PUVA and NB-UVB are effective for the treatment of vitiligo. However, NB-UVB has proved to have a distinct edge over PUVA in terms of better efficacy and lesser adverse effects.

The prevalence of vitamin D deficiency among dark-skinned populations according to their stage of migration and region of birth: A meta-analysis

ObjectivesThe prevalence of vitamin D deficiency (VDD) varies among migrants from different geographic regions. The aim of this study was to estimate the pooled prevalence of VDD among dark-skinned migrants. MethodA meta-analysis using meta-regression was undertaken to determine the prevalence of VDD in dark-skinned migrant populations. Prevalence also was determined by study characteristics including study methodology, age of populations examined, and length of time in migrated country. ResultsThirty-six studies were identified in nonpregnant populations. Of 13 974 individuals in the studies, 9562 were vitamin D deficient. Pooled prevalence in dark-skinned migrants, adjusted for latitude of study country was estimated at 77% (95% confidence interval [CI], 70%–84%). Examination of studies in which migrants from both Sub-Saharan Africa and the extended Middle East were examined (N = 7) showed immigrants from the extended Middle East had a higher prevalence of VDD (65%; 95% CI, 45%–94%) compared with those from Sub-Saharan Africa (56%; 95% CI, 34%–77%). Seven studies were identified in pregnant dark-skinned migrant women. This group tended to have much higher prevalence of VDD compared with native-born pregnant women. ConclusionImmigrants with dark skin, and in particular those from the extended Middle East region, have high prevalence of VDD. Migrants who are at high risk for VDD should be educated, screened, and monitored for VDD.

25-Hydroxyvitamin D in African-origin populations at varying latitudes challenges the construct of a physiologic norm , ,

The vitamin D-endocrine system is thought to play a role in physiologic processes that range from mineral metabolism to immune function. Serum 25-hydroxyvitamin D [25(OH)D] is the accepted biomarker for vitamin D status. Skin color is a key determinant of circulating 25(OH)D concentrations, and genes responsible for melanin content have been shown to be under strong evolutionary selection in populations living in temperate zones. Little is known about the effect of latitude on mean concentrations of 25(OH)D in dark-skinned populations. The objective was to describe the distribution of 25(OH)D and its subcomponents in 5 population samples of African origin from the United States, Jamaica, Ghana, South Africa, and the Seychelles. Participants were drawn from the Modeling of the Epidemiologic Transition Study, a cross-sectional observational study in 2500 adults, ages 25-45 y, enrolled between January 2010 and December 2011. Five hundred participants, ∼50% of whom were female, were enrolled in each of 5 study sites: Chicago, IL (latitude: 41°N); Kingston, Jamaica (17°N); Kumasi, Ghana (6°N); Victoria, Seychelles (4°S); and Cape Town, South Africa (34°S). All participants had an ancestry primarily of African origin; participants from the Seychelles trace their history to East Africa. A negative correlation between 25(OH)D and distance from the equator was observed across population samples. The frequency distribution of 25(OH)D in Ghana was almost perfectly normal (Gaussian), with progressively lower means and increasing skewness observed at higher latitudes. It is widely assumed that lighter skin color in populations outside the tropics resulted from positive selection, driven in part by the relation between sun exposure, skin melanin content, and 25(OH)D production. Our findings show that robust compensatory mechanisms exist that create tolerance for wide variation in circulating concentrations of 25(OH)D across populations, suggesting a more complex evolutionary relation between skin color and the vitamin D pathway.

A clinical study of the spectrum of photodermatoses in dark-skinned populations

Photodermatoses are characterized by an abnormal cutaneous response to 'ordinary' light exposure. To study the spectrum of photodermatoses in populations with dark skin (skin types IV-VI) at a tertiary referral centre. Consecutive patients with skin lesions confined to or predominantly located on photoexposed parts of the body and/or with photosensitivity were enrolled in the study, and their clinical details were recorded. Diagnosis was made on clinical grounds, and relevant investigations were carried out if required. Patch and photopatch testing were carried out in patients with chronic actinic dermatitis (CAD). Selected patients with CAD also underwent phototesting with UV (ultraviolet) A and broadband UVB light. We enrolled 362 patients (146 men, 216 women; mean age 35.6 ± 13.6 years), with mean disease duration of 3.4 years. The Fitzpatrick skin types were IV and V (52.8% and 47.2% of patients, respectively). Polymorphic light eruption (PMLE) was the commonest photodermatosis seen, affecting 59.7% of patients, followed by CAD (13.8%), collagen vascular disorders (7.7%), photoaggravated atopic dermatitis (6.1%), actinic lichen planus (ALP; 2.2%) and lichen planus pigmentosus (LPP; 1.6%). The majority (84.5%) of patients were involved in indoor work. Papular PMLE (37%) was the most common variant of PMLE, followed by pinpoint (31%), eczematous (22.2%), lichenoid (5.5%) and plaque-type (4.1%) PMLE. The spectrum of photodermatoses in Indian patients with dark skin phototypes (IV and V), is similar to that reported from other parts of the world. PMLE was the commonest photodermatosis seen, with the pinpoint and lichenoid variants accounting for over one-third of the PMLE cases. ALP and LPP were also not uncommon in our dark-skinned population.

The Andaman Islanders in a Regional Genetic Context: Reexamining the Evidence for an Early Peopling of the Archipelago from South Asia

The indigenous inhabitants of the Andaman Islands were considered by many early anthropologists to be pristine examples of a "negrito" substrate of humanity that existed throughout Southeast Asia. Despite over 150 years of research and study, questions over the extent of shared ancestry between Andaman Islanders and other small-bodied, gracile, dark-skinned populations throughout the region are still unresolved. This shared phenotype could be a product of shared history, evolutionary convergence, or a mixture of both. Recent population genetic studies have tended to emphasize long-term physical isolation of the Andaman Islanders and an affinity to ancestral populations of South Asia. We reexamine the genetic evidence from genome-wide autosomal single-nucleotide polymorphism (SNP) data for a shared history between the tribes of Little Andaman (Onge) and Great Andaman, and between these two groups and the rest of South and Southeast Asia (both negrito and non-negrito groups).

The Andaman Islanders in a Regional Genetic Context: Reexamining the Evidence for an Early Peopling of the Archipelago from South Asia

The indigenous inhabitants of the Andaman Islands were considered by many early anthropologists to be pristine examples of a “negrito” substrate of humanity that existed throughout Southeast Asia. Despite over 150 years of research and study, questions over the extent of shared ancestry between Andaman Islanders and other small-bodied, gracile, dark-skinned populations throughout the region are still unresolved. This shared phenotype could be a product of shared history, evolutionary convergence, or a mixture of both. Recent population genetic studies have tended to emphasize long-term physical isolation of the Andaman Islanders and an affinity to ancestral populations of South Asia. We reexamine the genetic evidence from genome-wide autosomal single-nucleotide polymorphism (SNP) data for a shared history between the tribes of Little Andaman (Onge) and Great Andaman, and between these two groups and the rest of South and Southeast Asia (both negrito and non-negrito groups).

The Andaman Islanders in a Regional Genetic Context: Reexamining the Evidence for an Early Peopling of the Archipelago from South Asia

The indigenous inhabitants of the Andaman Islands were considered by many early anthropologists to be pristine examples of a “negrito” substrate of humanity that existed throughout Southeast Asia. Despite over 150 years of research and study, questions over the extent of shared ancestry between Andaman Islanders and other small-bodied, gracile, dark-skinned populations throughout the region are still unresolved. This shared phenotype could be a product of shared history, evolutionary convergence, or a mixture of both. Recent population genetic studies have tended to emphasize long-term physical isolation of the Andaman Islanders and an affinity to ancestral populations of South Asia. We reexamine the genetic evidence from genome-wide autosomal single-nucleotide polymorphism (SNP) data for a shared history between the tribes of Little Andaman (Onge) and Great Andaman, and between these two groups and the rest of South and Southeast Asia (both negrito and non-negrito groups).

Economic and Social Factors in the Etiology of Childhood Rickets over the Past Four Centuries

Economic and social factors can determine the prevalence and severity of a health condition, as well as enhance co-morbidities. This article reviews forces that have influenced the appearance and persistence of nutritional rickets over the past 400 years. Childhood rickets first appeared from 1600 to 1640 as an epidemic disorder in the south and west of England when the woolen trade developed as a home labor industry. Later, with the coal-fueled factory system, agrarian laborers migrated to cities, creating a wage earner class. Their children were raised in smog-ridden and crowded conditions and were victims of an urban-based form of rickets lasting from the 1640s to the 1930s. With the discovery of vitamin D, arising from both dietary sources and from photocutaneous biosynthesis by exposure to ultraviolet B wavelengths from the sun, and recognition of its use as a therapeutic agent, epidemic rickets largely disappeared. The pro-sunshine era was ushered in between 1930 and 1965. Since, rising rates of skin cancer have greatly tempered enthusiasm for sun exposure and led to recommendations for sun protection strategies. Beginning in the 1960s, examples of nutritional rickets have been seen in dark-skinned immigrants moving to northern latitudes. Often rickets occurred in association with vitamin D-deficient mothers who exclusively breast-fed their offspring. Also, vitamin D deficiency is more evident in young children, adolescents, pregnant mothers and the elderly, many of who remain indoors and do not use vitamin supplements. These factors - child labor, the almost universal use of coal as a fuel, dietary deprivations during wars, migration of dark-skinned populations to regions where sunshine is scarce, and cancer-associated fear of sun exposure - have resulted in the persistence of nutritional rickets despite the knowledge of medical practitioners, nutritionists, and even parents. This manuscript reviews these factors and their impact on the health of children.

Skin Color Variation in Orang Asli Tribes of Peninsular Malaysia

Pigmentation is a readily scorable and quantitative human phenotype, making it an excellent model for studying multifactorial traits and diseases. Convergent human evolution from the ancestral state, darker skin, towards lighter skin colors involved divergent genetic mechanisms in people of European vs. East Asian ancestry. It is striking that the European mechanisms result in a 10–20-fold increase in skin cancer susceptibility while the East Asian mechanisms do not. Towards the mapping of genes that contribute to East Asian pigmentation there is need for one or more populations that are admixed for ancestral and East Asian ancestry, but with minimal European contribution. This requirement is fulfilled by the Senoi, one of three indigenous tribes of Peninsular Malaysia collectively known as the Orang Asli. The Senoi are thought to be an admixture of the Negrito, an ancestral dark-skinned population representing the second of three Orang Asli tribes, and regional Mongoloid populations of Indo-China such as the Proto-Malay, the third Orang Asli tribe. We have calculated skin reflectance-based melanin indices in 492 Orang Asli, which ranged from 28 (lightest) to 75 (darkest); both extremes were represented in the Senoi. Population averages were 56 for Negrito, 42 for Proto-Malay, and 46 for Senoi. The derived allele frequencies for SLC24A5 and SLC45A2 in the Senoi were 0.04 and 0.02, respectively, consistent with greater South Asian than European admixture. Females and individuals with the A111T mutation had significantly lighter skin (p = 0.001 and 0.0039, respectively). Individuals with these derived alleles were found across the spectrum of skin color, indicating an overriding effect of strong skin lightening alleles of East Asian origin. These results suggest that the Senoi are suitable for mapping East Asian skin color genes.