Grade-specific prostate cancer associations of IGF1 (CA)19 repeats and IGFBP3-202A/C in blacks and whites

Carrying the cytosine-adenosine (CA)19 repeat polymorphism in insulin-like growth factor-1 (IGF1) is associated with lower serum proteins and decreased prostate cancer risk. Carrying the -202A/C genotype in insulin-like growth factor binding protein-3 (IGFBP3) also has been associated with lower serum levels of the binding protein. However, the association between this variant and prostate cancer is inconsistent. To test the hypothesis that inconsistencies are partly due to cancer grade-specific differences in strength and direction of associations, we reanalyzed data from our previous Durham Veterans Administration Hospital study of blacks and whites comprising 47 cases (19 African Americans) with Gleason sum > or = 7, 50 cases (30 African Americans) with Gleason sum < 7 and 93 controls (49 African Americans). Compared to controls, the association between carrying the IGFBP3 C allele and prostate cancer risk was in OR(Low-Gleason) = 4.0; 95% CI: 1.4-12.3 compared to OR(High-Gleason) = 1.0; 95% CI: 0.4-2.2. Association patterns were similar in African Americans (OR(Low-Gleason) = 3.6; 95% CI: 1.0-13.2 vs. OR(High-Gleason) = 1.4; 95% CI: 0.4-2.3) and whites (OR(Low-Gleason) = 5.6; 95% CI: 0.6-49.0 vs. OR(High-Gleason) = 0.6; 95% CI: 0.2-2.2). The inverse association between carrying the IGF1 (CA)19 repeat variant did not vary by grade or ethnicity. If confirmed in larger studies, these findings support the hypothesis that the association between IGFBP3 C allele and prostate cancer is grade specific in both ethnic groups.     

SNORD116 and growth hormone therapy impact IGFBP7 in Prader–Willi syndrome

PurposePrader–Willi syndrome (PWS) is a neurodevelopmental disorder with hypothalamic dysfunction due to deficiency of imprinted genes located on the 15q11-q13 chromosome. Among them, the SNORD116 gene appears critical for the expression of the PWS phenotype. We aimed to clarify the role of SNORD116 in cellular and animal models with regard to growth hormone therapy (GHT), the main approved treatment for PWS.MethodsWe collected serum and induced pluripotent stem cells (iPSCs) from GH-treated PWS patients to differentiate into dopaminergic neurons, and in parallel used a Snord116 knockout mouse model. We analyzed the expression of factors potentially linked to GH responsiveness.ResultsWe found elevated levels of circulating IGFBP7 in naive PWS patients, with IGFBP7 levels normalizing under GHT. We found elevated IGFBP7 levels in the brains of Snord116 knockout mice and in iPSC-derived neurons from a SNORD116-deleted PWS patient. High circulating levels of IGFBP7 in PWS patients may result from both increased IGFBP7 expression and decreased IGFBP7 cleavage, by downregulation of the proconvertase PC1.ConclusionSNORD116 deletion affects IGFBP7 levels, while IGFBP7 decreases under GHT in PWS patients. Modulation of the IGFBP7 level, which interacts with IGF1, has implications in the pathophysiology and management of PWS under GHT.

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自身免疫性甲状腺疾病胰岛素样生长因子及其结合蛋白的改变

为探讨胰岛素样生长因子 (IGF )、胰岛素样生长因子结合蛋白 (IGFBP )在自身免疫性甲状腺疾病 (AITD )中的变化及其影响 ,本研究检测了 5 6例AITD患者与 2 4例正常对照血清IGF 1、IGFBP 1～ 3及甲状腺功能 ,发现IGF 1在GD、HT与GD控制组明显低于正常对照 (P <0 0 1) ,IGFBP 1、IGFBP 2在GD组明显高于正常对照 (P <0 0 1,0 0 5 ) ,IGFBP 3在HT组明显低于正常对照 (P <0 0 5 ) ;IGF 1与甲状腺激素间无相关 ,IGFBP 1～ 3均与TT4相关 (r =0 34、 0 38、 0 31;P <0 0 5 )。提示机体甲状腺激素、免疫状态均可能影响IGF、IGFBP水平 ,而后者有可能参与调节AITD的进程。     

Ethnic differences in low-density lipoprotein particle size in hypertensive adults

BackgroundHypertensive African Americans have higher rates of coronary heart disease (CHD) than their non-Hispanic white counterparts, despite having higher high-density lipoprotein cholesterol (HDL-C) levels and lower triglyceride levels.ObjectiveThe goal of the present study was to assess whether low-density lipoprotein (LDL) particle size, a correlate of the above lipid traits and a risk factor for CHD, differs between hypertensive African Americans and whites.MethodsParticipants included 1,177 hypertensive African Americans from Jackson, MS (60 ± 7 years, 72.4% women) and 860 hypertensive whites from Rochester, MN (58 ± 7 years, 56.7% women). LDL particle size was measured by polyacrylamide gradient gel electrophoresis. Within each gender, we assessed whether ethnicity was significantly associated with differences in LDL particle size after adjustment for CHD risk factors (age, total cholesterol, HDL-C, triglycerides, systolic blood pressure, diabetes, history of smoking, body mass index), statin use, and estrogen use (in women), and lifestyle variables (physical activity and alcohol intake).ResultsAlthough HDL-C levels were higher and triglyceride levels lower in African Americans, LDL particle size (adjusted for CHD risk factors) was lower (P < 0.0001) in African-American men and women than in their white counterparts (mean ± SD; men, 267.6 ± 5.2 Å vs 270.2 ± 4.8 Å; women 268.7 ± 5.1 Å vs 271.3 ± 5.1 Å). In both genders, African-American ethnicity was associated with lower LDL particle size after adjustment for CHD risk factors, statin use and estrogen use (in women), as well as physical activity and alcohol intake.ConclusionHypertensive African-American men and women have lower LDL particle size than their white counterparts, despite having higher HDL-C and lower triglycerides.     

IGF1 and IGFBP3 tagging polymorphisms are associated with circulating levels of IGF1, IGFBP3 and risk of breast cancer

Experimental and observational studies in humans and animals suggest that insulin-like growth factor 1 (IGF1) and its principal binding protein, IGFBP3, may influence breast cancer susceptibility. We have examined the association of nine and four single nucleotide polymorphisms (SNPs) in the IGF1 gene and in the IGFBP3 genes, respectively, with circulating levels of their gene products in a population-based study of 600 middle-aged men and women, and in a breast cancer case-control study, comprised 4647 cases and 4564 controls. All study participants are from the East Anglian region of UK. SNPs were specifically chosen to tag all other known SNPs in each gene. Several SNPs in each gene are associated both with circulating levels of their respective proteins and with risk of breast cancer. In particular, the c allele of IGF1 SNPrs1520220 is associated with increased circulating IGF1 (r2=2.1%, P-trend=0.003) in females and an increased risk of breast cancer: odds ratio (OR) (cc/gg)=1.41; 95% confidence intervals (95% CI) 1.11-1.79, P-trend=0.03. The a allele of IGFBP3 SNP rs2854744 is associated with increased circulating IGFBP3 (r2=9.7%, P<10(-9)) and a decreased risk of breast cancer: OR (aa/cc)=0.87; 95% CI 0.77-0.99, P=0.03. Our data indicate that common variants in the IGF1 and IGFBP3 genes are associated with differences in circulating levels of IGF1 and IGFBP3 and with breast cancer risk. More specifically and consistent with experimental models, our data suggest that higher IGF1 levels may increase the risk of breast cancer but higher IGFBP3 levels may be protective.     

Effect of race and predictors of socioeconomic status on diet quality in the HANDLS Study sample

PurposeTo examine effects of race and predictors of socioeconomic status (SES) on nutrient-based diet quality and their contribution to health disparities in an urban population of low SES.DesignData were analyzed from a sample of the Healthy Aging in Neighborhoods of Diversity Across the Life Span (HANDLS) Study participants examining effects of age, sex, race, income, poverty income ratio, education, employment, and smoking status on nutrient-based diet quality as measured by a micronutrient composite index of nutrient adequacy ratios and a mean adequacy ratio. Regression models were used to examine associations and t tests were used to look at racial differences.SubjectsAfrican American and white adults ages 30 to 64 years residing in 12 predefined census tracts in Baltimore, Maryland.ResultsSex, age, education, poverty income ratio, and income were statistically significant predictors of diet quality for African Americans, while sex, education, and smoking status were statistically significant for whites. African Americans had lower mean adequacy ratio scores than whites (76.4 vs 79.1). Whites had significantly higher nutrient adequacy ratios scores for thiamin, riboflavin, folate, B₁₂, vitamins A and E, magnesium, copper, zinc, and calcium, while African Americans had higher vitamin C scores.ConclusionEducation significantly impacted diet quality in the HANDLS sample, but race cannot be discounted. Whether the racial differences in diet quality are indicative of cultural differences in food preferences, selection, preparation, and availability, or disparities in socioeconomic status remains unclear.     

Long-term hypoxia exposure enhanced IGFBP-3 protein synthesis and secretion resulting in cell apoptosis in H9c2 myocardial cells

Abstract

Myocardial infarction (MI) usually results in myocardial ischemia, remodeling and hypoxia that lead to cell death. To date, the insulin-like growth factor binding protein-3 (IGFBP3) is known to play an important role in insulin growth factor (IGF) bioavailability. Previous studies have found that hypoxia results in cell apoptosis. However, the detailed mechanism and roles of IGFBP3 in long-term hypoxia (LTH) regulated heart cell apoptosis remains unknown. In this study H9c2 cardiomyoblast cells were treated with investigated long-term hypoxic exposure with the possible mechanisms involved. The results showed that LTH enhanced IGFBP3 protein synthesis and induced its secretion. The accumulated IGFBP3 sequestered Insulin growth factor 1 (IGF-1) away from the type I IGF receptor (IGF-1?R), which blocked the IGF1R/PI3K/Akt survival signaling pathway, resulting in cell apoptosis. According to our findings, IGFBP3 could be a valuable target for developing treatments for cardiac diseases in long-term hypoxia exposure patients.     

Incorporating ethnicity into genetic risk assessment for Alzheimer disease: the REVEAL study experience

PurposeTo describe how investigators in a multisite randomized clinical trial addressed scientific and ethical issues involved in creating risk models based on genetic testing for African American participants.MethodsThe following informed our decision whether to stratify risk assessment by ethnicity: evaluation of epidemiological data, appraisal of benefits and risks of incorporating ethnicity into calculations, and feasibility of creating ethnicity-specific risk curves. Once the decision was made, risk curves were created based on data from a large, diverse study of first-degree relatives of patients with Alzheimer disease.ResultsReview of epidemiological data suggested notable differences in risk between African Americans and whites and that Apolipoprotein E genotype predicts risk in both groups. Discussions about the benefits and risks of stratified risk assessments reached consensus that estimates based on data from whites should not preclude enrolling African Americans, but population-specific risk curves should be created if feasible. Risk models specific to ethnicity, gender, and Apolipoprotein E genotype were subsequently developed for the randomized clinical trial that oversampled African Americans.ConclusionThe Risk Evaluation and Education for Alzheimer Disease study provides an instructive example of a process to develop risk assessment protocols that are sensitive to the implications of genetic testing for multiple ethnic groups with differing levels of risk.     

A Microsatellite Polymorphism in IGF1 Gene Promoter and Timing of Natural Menopause in Caucasian Women

Background: Genes involved in the IGF-1 aging pathways in the human ovary can be considered strong candidates for predictors of the natural menopause timing. This study evaluates the association between a cytosine-adenine (CA) microsatellite polymorphism in the IGF1 gene promoter P1 and age at natural menopause.Methods: Genomic DNA was extracted from the peripheral blood, PCR was performed using primers designed to amplify the polymorphic (CA)_n repeat of the human IGF1 gene, an allele dose effect for the most common (CA)19 repeats allele, Cox proportional hazard regression models and the Kaplan-Meier cumulative survivorship method with the log-rank test were used to determine statistical significance of studied associations in a sample of 257 Polish women aged 40-58 years.Results: Crude Cox proportional hazard regression analysis confirmed the association between the IGF1 gene polymorphism and the menopause timing (p=0.038). This relationship remained statistically significant after controlling for other menopause confounders in multivariate modelling. Out of the input variables, the (CA)_n polymorphism in the IGF1 gene promoter, age at menarche and smoking status were independent covariates of the natural menopause timing (χ² =12.845; df=3; p=0.034). The onset of menopause at a younger age was likely associated with the IGF1 genotype variant not carrying the (CA)19 repeats allele, menarche before the age of 12 and a current cigarette smoker status (HR=1.6).Conclusion: This study provides evidence that a common cytosine-adenine (CA) microsatellite repeat polymorphism in the P1 promoter region of the IGF1 gene is an independent predictive factor for age at natural menopause in Caucasian women also after adjusting for other menopause covariates.     

African American ancestry contribution to asthma and atopic dermatitis

ObjectiveAsthma and atopic dermatitis (AD) are complex diseases with striking disparities across racial and ethnic groups, which may be partly attributable to genetic factors. Here we summarize current knowledge from asthma and AD genome-wide association studies (GWAS) and pharmacogenetic studies in African ancestry populations.Data SourcesGWAS catalog; PUBMed.Study SelectionsGWAS catalog studies with trait annotations “asthma” and “atopic eczema” and African ancestry individuals in the discovery dataset; the recent CAAPA asthma GWAS; reports on pharmacogenetic studies in asthma and AD.ResultsAlthough GWASs have revolutionized gene discovery for multiple complex traits, African Americans continue to be severely underrepresented in sufficiently powered genetics studies. Indeed, of the 16 asthma and 21 AD loci that reached genomewide significance in Europeans, very few have replicated in African ancestry populations. Challenges in comparing results from European vs African ancestry cohorts include modest sample size, differences in risk allele frequency, effect size, correlation between genetic variants, and environmental exposure in evolutionary history. African Americans also constitute a small percentage of dermatological and respiratory-focused clinical trials. Pharmacogenetic studies have similarly been focused largely on non-Hispanic whites, despite compelling evidence that genetic variation from different ancestral backgrounds may alter therapeutic efficacy of asthma and AD drugs.ConclusionLarge-scale genetic studies of asthma and AD in African Americans are essential to reduce research and health disparities and empower scientific discoveries.     

The androgen receptor CAG and GGN repeat polymorphisms and prostate cancer susceptibility in African-American men: results from the Flint Men’s Health Study

Repeat lengths of the CAG and GGN microsatellites in exon 1 of the androgen receptor (AR) gene have been hypothesized to be associated with prostate cancer risk. In vitro studies have showed an inverse association between AR CAG and GGN repeat length and activity levels of the AR product. It is known that men of African descent have a higher incidence of and greater mortality from prostate cancer than men of Caucasian or Asian descent and, on average, a smaller number of repeats at AR CAG and GGN. Consistent with these findings, studies have also found increased AR protein expression levels in benign prostatic hyperplasia and prostatic diseased tissues from men of African descent. Despite these findings, limited studies have been conducted to evaluate the association between repeat lengths at AR CAG and prostate cancer risk in African Americans. Our study is the first such study to examine whether repeat length of the AR GGN repeat is associated with prostate cancer risk in African Americans. We found no evidence for an association between AR CAG or GGN repeat lengths and prostate cancer risk in a population-based sample of African Americans.     

A comparison of pathomolecular markers of fibrosis and morphology in kidney from autopsies of African Americans and whites

African Americans have an increased incidence of chronic kidney disease (CKD) due to hypertension and arteriosclerosis and increased death due to coronary artery disease, compared with whites. The pathogenesis of CKD involves the increased presence and activation of myofibroblasts and macrophages, promotion of tubulointerstitial fibrosis, and effects of tubulointerstitial cell mitosis and apoptosis. We hypothesized that increased risk of hypertensive vascular disease may be identified by renal pathomolecular markers that are associated with progressive CKD. Renal sections were available from 50 autopsies of 33 African Americans (55% males) and 17 whites (76% males) undergoing forensic autopsy for unexpected death. Sclerotic glomeruli, severity of cortical fibrosis, and renal arteriolosclerosis, total glomerular number (N _glom), average glomerular volume (V _glom), birth weights, and blood pressure were known. Presence and locality of markers for myofibroblasts (alpha-SMA), macrophages (CD68), collagen, pro-fibrotic transforming growth factor-beta1 were scored in renal autopsies, and tubulointerstitial apoptosis was recorded. The results demonstrated a strong positive correlation between age, cortical fibrosis and alpha-SMA (p < 0.05), and between CD68 and hypertension and coronary artery disease (p < 0.05). The findings confirm the role of myofibroblasts and macrophages in pathogenesis of human CKD. However, the markers showed no significant relationships to V _glom, N _glom, birth weight, or race.     

Gender differences in the insulin-like growth factor axis response to a glucose load

Aims: The insulin‐like growth factors (IGFs) are thought to contribute to glucose homeostasis. The aim of our study was to examine the response of the IGFs and their binding proteins to an intravenous load of glucose in a cohort of young men and women with normal glucose tolerance. Methods: The intravenous glucose tolerance test (IVGTT) was used to quantify insulin sensitivity and insulin secretion in 160 adults aged 20–21 years in Adelaide, Australia. Serum IGF‐I, IGF‐II, IGF‐binding protein (IGFBP)‐1 and IGFBP‐3 were measured during the IVGTT. Results: Women were less insulin sensitive than men with higher fasting insulin (women 55.6 ± 4.4, men 44.1 ± 3.6 pmol L^?1, P = 0.001) and first phase insulin secretion (women 3490 ± 286, men 3038 ± 271 pmol L^?1 min, P = 0.042). Women showed lower fasting free IGF‐I (women 0.29 ± 0.02, men 0.36 ± 0.02 μg L^?1, P = 0.004) but higher IGFBP‐3 (women 46.3 ± 0.53, men 43.3 ± 0.58 mg dL^?1, P = 0.001) and higher IGFBP‐1 concentrations (women 37.0 ± 2.9, men 24.8 ± 2.3 μg L^?1, P = 0.012). IGFBP‐1 fell by 5 min and remained suppressed. IGFBP‐3 and total IGF‐I fell until 60 min rising again by 2 h. IGF and IGFBP values were all higher in women. IGFBP‐1 showed a negative association with fasting and stimulated insulin concentrations in both genders. First phase insulin secretion however showed positive correlations with IGFBP‐3 (r = 0.321, P = 0.004) and IGF‐I (r = 0.339 P = 0.002) in men but not women. Conclusion: Our data show that IGFBP‐1, IGFBP‐3 and IGF‐I show acute changes following a glucose load and there are marked gender differences in these responses.     

Genetic variation in insulin-like growth factor 2 may play a role in ovarian cancer risk

The insulin-like growth factor (IGF) signaling axis plays an important role in cancer biology. We hypothesized that genetic variation in this pathway may influence risk of ovarian cancer. A three-center study of non-Hispanic whites including 1880 control women, 1135 women with invasive epithelial ovarian cancer and 321 women with borderline epithelial ovarian tumors was carried out to test the association between tag single-nucleotide polymorphisms (tSNPs) (n=58) in this pathway and risk of ovarian cancer. We found no association between variation in IGF1, IGFBP1 or IGFBP3 and risk of invasive disease, whereas five tSNPs in IGF2 were associated with risk of invasive epithelial ovarian cancer at P<0.05 and followed-up one of the associated SNPs. We conducted genotyping in 3216 additional non-Hispanic white cases and 5382 additional controls and were able to independently replicate our initial findings. In the combined set of studies, rs4320932 was associated with a 13% decreased risk of ovarian cancer per copy of the minor allele carried (95% confidence interval 0.81-0.93, P-trend=7.4 × 10(-5)). No heterogeneity of effect across study centers was observed (p(het)=0.25). IGF2 is emerging as an important gene for ovarian cancer; additional genotyping is warranted to further confirm these associations with IGF2 and to narrow down the region harboring the causal SNP.     

Racial variation in colorectal polyp and tumor location

OBJECTIVES: The incidence and mortality from colorectal cancer among whites have decreased, but they have remained unchanged among African Americans. To explain this disparity, we used the multicenter endoscopy database of the Clinical Outcomes Research Initiative to compare the prevalence of proximal polyps and tumors among asymptomatic African Americans and whites undergoing routine screening colonoscopy. METHODS: African Americans and whites undergoing colonoscopy between January 1, 2002 and September 30, 2003 were considered for analysis. RESULTS: There were 145,175 index colonoscopy reports on unique patients. After applying exclusion criteria, 46,726 patients remained for analysis. Adjusting for age, gender, American Society of Anesthesiologists level, bowel preparation and endoscopic setting, African Americans were less likely to have polyps [adjusted odds ratio (OR) = 0.77; 95% confidence interval (CI) = 0.70-0.84]. However, the odds of having proximal polyps was higher in African Americans (OR = 1.30; 95% CI: 1.11-1.52) compared to whites. In regards to tumors, African Americans were more likely to have tumors (OR = 1.78; 95% CI: 1.14-2.77) and more likely to have proximal tumors than whites (OR = 4.37; 95% CI: 1.16-16.42). CONCLUSIONS: After adjusting for confounders, African Americans undergoing screening colonoscopy in multiple practice settings had higher odds of proximal polyps and tumors than whites, suggesting current colorectal cancer screening recommendations in African Americans should be expanded.     

Behavioral Treatment of Hypertensive Heart Disease in African Americans: Rationale and Design of a Randomized Controlled Trial

Abstract

African Americans experience higher morbidity and mortality than Whites do as a result of hypertension and associated cardiovascular disease. Chronic psychosocial stress has been considered an important contributing factor to these high rates. The authors describe the rationale and design for a planned randomized controlled trial comparing Transcendental Meditation, a stress-reduction technique, with lifestyle education in the treatment of hypertension and hypertensive heart disease in urban African Americans. They pretested 170 men and women aged 20 to 70 years over a 3-session baseline period, with posttests at 6 months. Outcomes included clinic and ambulatory blood pressure, quality of life, left ventricular mass measured by M-mode echocardiography, left ventricular diastolic function measured by Doppler, and carotid atherosclerosis measured by β-mode ultrasound. This trial was designed to evaluate the hypothesis that a selected stress reduction technique is effective in reducing hypertension and hypertensive heart disease in African Americans.     

Association between increased levels of TNF-alpha, decreased levels of prealbumin and retinol-binding protein, and disease outcome

We determined whether there is an association between tumor necrosis factor-alpha (TNF-alpha), undernutrition [prealbumin (PA) <160 mg/L, retinol binding protein (RBP) <30 mg/L], disease stage, outcome (death or survival), and race in children with leukemia. TNF-alpha, PA, and RBP were measured in 52 patients (0.8 to 17 years old): 18 African Americans, 34 whites; 27 newly diagnosed (ND), and 25 in clinical remission (CR). Mean levels of TNF-alpha were higher in patients than in 46 healthy children (p < 0.05), but were not different between ND and CR groups. Mean acute phase proteins (APP) were different among groups: ND > CR > controls (p < 0.05). Mean levels of PA and RBP were lower in patients than in controls (p < 0.051, and tended to be higher in CR than in ND patients. African-American patients had lower concentrations of TNF-alpha, PA, and RBP but higher APP than white patients (p < 0.05). CR patients and African-American patients who died tended to have higher levels of TNF-alpha and APP, but lower PA and RBP than those who survived. A higher percentage of ND African Americans (45%) than of ND whites (13%) died. Results suggest that undernutrition and inflammation in CR patients and African Americans were associated with poor survival, and that ND African Americans have a poorer outcome than whites independently of TNF-alpha levels.     

Insulin-like growth factors and their binding proteins in the venous effluents of ovary and adrenal gland in severely hyperandrogenic women

Insulin and insulin-like growth factors (IGF) are thought to play an important role in the pathogenesis of excessive androgen production. To explore this question further we measured the concentrations of IGF-I and -II and their binding proteins (IGFBP-1 and-3) in adrenal and ovarian vein samples of severely hyperandrogenic women (serum testosterone > 5 nmol/l) collected as part of their diagnostic work-up. The concentration of IGF-II was slightly but not significantly higher in the ovarian vein than in the adrenal and peripheral veins. The concentrations of IGF-I and IGFBP were identical in both the adrenal and ovarian veins and did not differ from those in the peripheral circulation. The concentration of IGFBP-1 was negatively correlated (r = -0.60, P > 0.05) with insulin and IGFBP-3 showed a strong positive correlation with IGF-1 (r = 0.90, P > 0.01). These results indicate that neither the ovary nor the adrenal gland contributes significantly to the circulating pool of IGF or their binding proteins in severely hyperandrogenic subjects. Hyperinsulinaemia is associated with low circulating IGFBP-1 concentrations and IGFBP-3 seems to be an excellent indicator of the peripheral IGF-I concentration. The concentrations of IGF-I suggested decreased somatotrophic activity in these obese, hyperinsulinaemic subjects.      

Minority donation in the United States

Background and Objective  In the United States, approximately 15 million whole blood products are collected each year from 10 million volunteer donors. African Americans are underrepresented in the donor pool. In 2008, 7% of white versus 4% of African American and Hispanics adults donated in the previous year. The donor rates vary by region in the United States: 77–93% for whites, 1–16% for African Americans and 1–13% for Hispanics. In the Atlanta metropolitan area whose donor pool is 77% white, 16% African American and 4% Hispanic, the blood donor rate (number of blood donors per population) was 11/1000 population for whites, 6/1000 for African Americans and 3/1000 population for Hispanics; and the blood donation rate (number of units donated by population over the total population) was 77 donations/1000 population for whites, 22/1000 population for African Americans and 10/1000 population for Hispanics. Thus, African Americans and Hispanics represent half of the donors as whites when adjusted for their percentage of the population and more strikingly donate a significantly fewer number of units per each donor. Materials and Methods  Literature on reasons for racial/ethnic differences in donation rates and methods to address these differences was reviewed. Results  The reasons for these differences are multifactorial. First, although 41% of the total US population is estimated to be eligible to donate, African Americans and Hispanics have lower eligibility rates (whites 46%, African Americans 36%, and Hispanics 41%). Second, donor deferral rates are higher for minorities: whites 11%, African Americans 18%, Hispanics 14% and Asians 16%. Deferral is most commonly secondary to temporary deferral reasons such as low hemoglobin level, yet donors are less likely to return once deferred, and thus deferral affects donor and donation rates. Third, minorities may have different motivators and barriers. The most cited motivators to blood donation are more convenient place and times, and being asked; and the most cited barriers are fear of catching a disease and feeling faint/dizzy, and not have time or knowing where to donate. Racial differences in motivating factors identified include African Americans are more likely than whites to donate to receive an item/gift and be tested for infectious disease, and if assured that donating is safe. Notably, these motivators are not the primary cited motivators. African Americans compared with whites more commonly cite fear, difficulty finding veins and not knowing where to donate as deterrents. In addition, African Americans have distrust in the healthcare system, which is correlated with lower donation rates. Fourth, different racial/ethnic groups may have different preferred marketing strategies, including methods of contact, as well as culturally specific motivators for behavioural change. Conclusion  Thus, with an improved understanding of these differences as well as accurate tools to measure the outcomes, culturally targeted recruitment programs can be developed to increase donation rates.