scholarly journals Genetic loci associated with skin pigmentation in African Americans and their effects on vitamin D deficiency

PLoS Genetics ◽  
2021 ◽  
Vol 17 (2) ◽  
pp. e1009319
Author(s):  
Ken Batai ◽  
Zuxi Cui ◽  
Amit Arora ◽  
Ebony Shah-Williams ◽  
Wenndy Hernandez ◽  
...  
Keyword(s):  
Vitamin D ◽  
African Americans ◽  
Vitamin D Deficiency ◽  
Genome Wide Association Study ◽  
African Ancestry ◽  
Skin Pigmentation ◽  
Genetic Score ◽  
Genome Wide ◽  
Melanin Index ◽  
25 Oh Vitamin D

A recent genome-wide association study (GWAS) in African descent populations identified novel loci associated with skin pigmentation. However, how genomic variations affect skin pigmentation and how these skin pigmentation gene variants affect serum 25(OH) vitamin D variation has not been explored in African Americans (AAs). In order to further understand genetic factors that affect human skin pigmentation and serum 25(OH)D variation, we performed a GWAS for skin pigmentation with 395 AAs and a replication study with 681 AAs. Then, we tested if the identified variants are associated with serum 25(OH) D concentrations in a subset of AAs (n = 591). Skin pigmentation, Melanin Index (M-Index), was measured using a narrow-band reflectometer. Multiple regression analysis was performed to identify variants associated with M-Index and to assess their role in serum 25(OH)D variation adjusting for population stratification and relevant confounding variables. A variant near the SLC24A5 gene (rs2675345) showed the strongest signal of association with M-Index (P = 4.0 x 10−30 in the pooled dataset). Variants in SLC24A5, SLC45A2 and OCA2 together account for a large proportion of skin pigmentation variance (11%). The effects of these variants on M-Index was modified by sex (P for interaction = 0.009). However, West African Ancestry (WAA) also accounts for a large proportion of M-Index variance (23%). M-Index also varies among AAs with high WAA and high Genetic Score calculated from top variants associated with M-Index, suggesting that other unknown genomic factors related to WAA are likely contributing to skin pigmentation variation. M-Index was not associated with serum 25(OH)D concentrations, but the Genetic Score was significantly associated with vitamin D deficiency (serum 25(OH)D levels less than 12 ng/mL) (OR, 1.30; 95% CI, 1.04–1.64). The findings support the hypothesis suggesting that skin pigmentation evolved responding to increased demand for subcutaneous vitamin D synthesis in high latitude environments.

scholarly journals Vitamin D deficiency increases prostatic megalin expression and globulin-bound testosterone import, increasing prostatic androgens in African American men

2021 ◽  
Author(s):  
Jason Garcia ◽  
Kirsten Krieger ◽  
Candice Loitz ◽  
Lillian M Perez ◽  
Zachary A Richards ◽  
...  
Keyword(s):  
Vitamin D ◽  
African American ◽  
African Americans ◽  
Vitamin D Deficiency ◽  
African American Men ◽  
African Ancestry ◽  
Serum Vitamin ◽  
Vitamin D Metabolites ◽  
Increased Risk ◽  
Vitamin D Levels

Vitamin D deficiency associates with an increased risk of prostate cancer (PCa) mortality and is hypothesized to contribute to PCa aggressiveness and disparities in African Americans. We reported a relationship between African-ancestry, circulating and intraprostatic vitamin D metabolites and prostatic expression of megalin, an endocytic membrane receptor that internalizes globulin-bound hormones. Here, we show that megalin imports sex hormone-binding globulin (SHBG)-bound testosterone, potentially regulating intraprostatic hormone levels. Vitamin D levels regulated megalin expression in cell lines, patient-derived prostate epithelial cells, and prostate tissue explants, and mice with prostatic knockout of Lrp2 (megalin) showed reduced prostatic testosterone. Notably, prostatic 5α-dihydrotestosterone levels were higher in African American men and correlated inversely with serum vitamin D status, while megalin protein levels were reduced in PCa tissue. Our findings highlight the negative impact of vitamin D deficiency on PCa and the potential link to PCa disparities observed in African Americans.

scholarly journals Genetic ancestry, skin reflectance and pigmentation genotypes in association with serum vitamin D metabolite balance

2011 ◽  
Vol 7 (1) ◽  
Author(s):  
Robin Taylor Wilson ◽  
Alanna N. Roff ◽  
P. Jenny Dai ◽  
Tracey Fortugno ◽  
Jonathan Douds ◽  
...  
Keyword(s):  
Vitamin D ◽  
African Ancestry ◽  
Skin Pigmentation ◽  
Serum Vitamin ◽  
Genetic Ancestry ◽  
Vitamin D Metabolites ◽  
Serum Vitamin D ◽  
Skin Reflectance ◽  
Melanin Index ◽  
American Heritage

AbstractLower serum vitamin D (25(OH)D) among individuals with African ancestry is primarily attributed to skin pigmentation. However, the influence of genetic polymorphisms controlling for skin melanin content has not been investigated. Therefore, we investigated differences in non-summer serum vitamin D metabolites according to self-reported race, genetic ancestry, skin reflectance and key pigmentation genes (Healthy individuals reporting at least half African American or half European American heritage were frequency matched to one another on age (±2 years) and sex. One hundred and seventy-six autosomal ancestry informative markers were used to estimate genetic ancestry. Melanin index was measured by reflectance spectrometry. Serum vitamin D metabolites [25(OH)DFifty African Americans and 50 European Americans participated in the study. Compared withThe

scholarly journals Eyes of Africa: The Genetics of Blindness: Study Design and Methodology

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Olusola Olawoye ◽  
Chimdi Chuka-Okosa ◽  
Onoja Akpa ◽  
Tony Realini ◽  
Michael Hauser ◽  
...  
Keyword(s):  
Genome Wide Association Study ◽  
Case Control Study ◽  
African Ancestry ◽  
Collaborative Study ◽  
Data Set ◽  
Human Heredity ◽  
Genome Wide ◽  
A Genome ◽  
Multiplex Families ◽  
Control Study

Abstract Background This report describes the design and methodology of the “Eyes of Africa: The Genetics of Blindness,” a collaborative study funded through the Human Heredity and Health in Africa (H3Africa) program of the National Institute of Health. Methods This is a case control study that is collecting a large well phenotyped data set among glaucoma patients and controls for a genome wide association study. (GWAS). Multiplex families segregating Mendelian forms of early-onset glaucoma will also be collected for exome sequencing. Discussion A total of 4500 cases/controls have been recruited into the study at the end of the 3rd funded year of the study. All these participants have been appropriately phenotyped and blood samples have been received from these participants. Recent GWAS of POAG in African individuals demonstrated genome-wide significant association with the APBB2 locus which is an association that is unique to individuals of African ancestry. This study will add to the existing knowledge and understanding of POAG in the African population.

scholarly journals Identification of unique venous thromboembolism-susceptibility variants in African-Americans

2017 ◽  
Vol 117 (04) ◽  
pp. 758-768 ◽  
Author(s):  
Sebastian Armasu ◽  
Bryan McCauley ◽  
Iftikhar Kullo ◽  
Hugues Sicotte ◽  
Jyotishman Pathak ◽  
...  
Keyword(s):  
Gene Expression ◽  
Venous Thromboembolism ◽  
African Americans ◽  
Differential Expression ◽  
White Women ◽  
Genome Wide Association Study ◽  
Expression Data ◽  
Significant Differential Expression ◽  
Genome Wide ◽  
A Genome

SummaryTo identify novel single nucleotide polymorphisms (SNPs) associated with venous thromboembolism (VTE) in African-Americans (AAs), we performed a genome-wide association study (GWAS) of VTE in AAs using the Electronic Medical Records and Genomics (eMERGE) Network, comprised of seven sites each with DNA biobanks (total ~39,200 unique DNA samples) with genome-wide SNP data (imputed to 1000 Genomes Project cosmopolitan reference panel) and linked to electronic health records (EHRs). Using a validated EHR-driven phenotype extraction algorithm, we identified VTE cases and controls and tested for an association between each SNP and VTE using unconditional logistic regression, adjusted for age, sex, stroke, site-platform combination and sickle cell risk genotype. Among 393 AA VTE cases and 4,941 AA controls, three intragenic SNPs reached genome-wide significance: LEMD3 rs138916004 (OR=3.2; p=1.3E-08), LY86 rs3804476 (OR=1.8; p=2E-08) and LOC100130298 rs142143628 (OR=4.5; p=4.4E-08); all three SNPs validated using internal cross-validation, parametric bootstrap and meta-analysis methods. LEMD3 rs138916004 and LOC100130298 rs142143628 are only present in Africans (1000G data). LEMD3 showed a significant differential expression in both NCBI Gene Expression Omnibus (GEO) and the Mayo Clinic gene expression data, LOC100130298 showed a significant differential expression only in the GEO expression data, and LY86 showed a significant differential expression only in the Mayo expression data. LEMD3 encodes for an antagonist of TGF-β-induced cell proliferation arrest. LY86 encodes for MD-1 which down-regulates the pro-inflammatory response to lipopolysaccharide; LY86 variation was previously associated with VTE in white women; LOC100130298 is a non-coding RNA gene with unknown regulatory activity in gene expression and epigenetics.Supplementary Material to this article is available online at www.thrombosis-online.com.

Abstract 121: Vitamin D Deficiency Study in Postural Orthostatic Tachycardia Syndrome

2015 ◽  
Vol 8 (suppl_2) ◽  
Author(s):  
Chandralekha Ashangari ◽  
Amer Suleman
Keyword(s):  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Electronic Medical Records ◽  
Vitamin D3 ◽  
Medical Records ◽  
Postural Orthostatic Tachycardia Syndrome ◽  
Vitamin D Levels ◽  
The World ◽  
25 Oh Vitamin D ◽  
Vitamin D3 Deficiency

Objectives The aim of this study is to assess vitamin D levels, including the prevalence of vitamin D deficiency/insufficiency in Postural Orthostatic Tachycardia Syndrome (POTS) patients. Background : The Postural Orthostatic Tachycardia Syndrome (POTS) affects primarily young women. POTS is a form of dysautonomia that is estimated to impact between 1,000,000 and 3,000,000 Americans, and millions more around the world. We frequently find vitamin D deficiency in patients who present with POTS Methods: 180 patients were selected randomly from our clinic with POTS. Patients Vitamin D levels charts were reviewed from electronic medical records, 25-OH vitamin D (Vitamin D3 ) status was defined as Normal (>30 ng/mL), Insufficient (20.0-29.9 ng/mL), and deficient (<20 ng/mL). Results: Out of 180 patients, 170 patients are female (94%, n=170, age 31.88±10.36), 10 patients are male (6% ,age 25.83±6.19). 79 patients had vitamin D3 level >30 ng/ml, 10 patients had vitamin D3 level range >20.0 to 29.9 ng/mL, 91 patients had vitamin D3 level < 20ng/mL. Conclusion: Our research results demonstrated that Postural Orthostatic Tachycardia Syndrome (POTS) patients have a higher rate of vitamin D3 deficiency (51% have Vitamin D3 less than 20 ng/mL). Vitamin D3 levels are low in more than half of POTS patients (56% had less than 30 ng/mL )

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