Caucasian Individuals Research Articles

A new HLA-B*39 allele, B*39:168, closely related to B*39:05:01:02.

A new HLA-B*39:168 was characterized in a Caucasian Spanish individual.

Visceral Adiposity and Glucoregulatory Peptides are Associated with Susceptibility to Type 2 Diabetes: The TOFI_Asia Study.

Ethnic differences in fat deposition contribute to type 2 diabetes (T2D). Identification of biomarkers that underpin dysglycemia are needed for better-targeted prevention and treatment. The cross-sectional thin-on-the-outside-fat-on-the-inside (TOFI)_Asia study investigated adipose depots and clinical biomarkers as predictors of fasting plasma glucose (FPG) and insulin resistance (IR; assessed using the updated homeostatic model assessment of IR) in lean and overweight normo- and dysglycemic Chinese (n = 199) and Caucasian (n = 158) individuals. Multivariate least-angle regression models were used to identify predictors of FPG and IR. At similar age and BMI, Chinese individuals had lower body weight but had a greater percentage of total abdominal adipose tissue and a greater percentage of total visceral adipose tissue (VAT) (all P < 0.005). In Chinese individuals, FPG, hemoglobin A1c , fasting insulin, and triglycerides were higher, whereas HDL cholesterol and total and high-molecular-weight adiponectin levels were lower (all P < 0.0001). Raised liver enzyme and peptide concentrations (P < 0.02) were consistent with increased T2D risk. Lean Chinese women (<25 kg/m2 ) had greater total abdominal adipose tissue (kilograms) and VAT (kilograms) than Caucasian women, exhibiting the TOFI profile, with raised FPG (P < 0.001) and IR (P = 0.01). Risk factors for elevated FPG specific to Chinese individuals included male gender, VAT, and triglycerides (R2 = 0.33), and risk factors for IR specific to Chinese individuals included amylin, C-peptide, and glucagon (R2 = 0.49). VAT, amylin, and C-peptide were predictors in Caucasian individuals. VAT contributed to dysglycemia in both ethnicities, particularly in Chinese individuals characterized by the TOFI phenotype, as did the glucoregulatory peptides amylin and C-peptide, providing targets for T2D prevention.

Are Conditional Sentence Orders Used Differently for Indigenous Offenders? A Comparison of Sentences and Outcomes in Canada

Conditional sentence orders (CSOs) were introduced in Canada in 1996, largely as a mechanism to address the overreliance on incarceration. This sentencing option is particularly relevant for Indigenous individuals who have been vastly overrepresented in custodial settings. Despite being in place for over twenty years, little is known about the use and effectiveness of CSOs. The current study examined the use and outcomes of CSOs for Indigenous (n = 749) and non-Indigenous offenders (n = 1,625) in one Canadian province. Specifically, the length of CSO, frequency and type of optional conditions, number of breaches, and rates of reoffending were compared between the two groups. Results from a logistic regression, controlling for risk relevant co-variates, indicated that Indigenous individuals tended to receive shorter CSOs compared to Caucasian individuals. However, Indigenous individuals were 35% more likely than Caucasian individuals to be convicted of a breach and more likely to incur multiple breaches while on a CSO. Despite the differences in the rates of breaches, the likelihood of reoffending over a two-year period was equivalent across the two groups. Although the reasons for breach were not available for the current study, future research should investigate this further to determine whether increased breach rates for Indigenous individuals are the result of more rule-violating behaviour, an inequity in the fairness of the conditions applied to Indigenous versus Caucasian individuals, or whether it is possible that breaches are over-detected and convicted at a higher rate for Indigenous individuals. Greater awareness of the underlying mechanisms related to increased breach rates affords the opportunity to ensure that CSOs are consistently implemented, something which will contribute to achieving the objective of successful diversion from imprisonment.

Assessment of Racial/Ethnic Disparities in Volumetric MRI Correlates of Clinical Disability in Multiple Sclerosis: A Preliminary Study.

Although global and regional brain volume has been established as a relevant measure to define and predict multiple sclerosis (MS) severity, characterization of specific trends by race/ethnicity is currently lacking. We aim to (1) characterize racial disparities in disability-specific patterns of brain MRI volumetric measures between Hispanic and Caucasian individuals with MS and (2) explore the relevance of these measures as predictors of clinical disability progression. Brain MRI scans from 94 Hispanic and 94 age- and gender-matched Caucasian MS patients were analyzed using automatic and manual segmentation techniques. Select global and regional volume measures were correlated to Expanded Disability Status Scale (EDSS) scores at baseline and subsequent follow-up visits. Hispanic patients had a higher baseline median EDSS score (interquartile range [IQR], 2.0; [1.0-3.5]) compared to Caucasians (median [IQR], 1.0 [.0-2.0]) and an increased risk of requiring ambulatory assistance (hazard ratio [HR], 9.7; 95% confidence interval [CI], 2.8-32.5). Normalized thalamic volume was moderately associated with EDSS scores (rs = -.42, P < .001 in Hispanics;rs = -.32,P = .002 in Caucasians) and was the best predictor of sustained disability worsening in both racial groups in a time-to-event analysis. The confounding impact of race on quantitative brain volume measures may affect the interpretation of outcome measures in MS clinical trials.

Higher Febuxostat Exposure Observed in Asian Compared with Caucasian Subjects Independent of Bodyweight.

Febuxostat is a xanthine oxidase inhibitor indicated for gout and hyperuricemia. This work investigates potential clinically relevant covariates for febuxostat pharmacokinetics with a special focus on Asian race and bodyweight. Febuxostat plasma concentrations from 141 male subjects were obtained from two phase II studies in patients with hyperuricemia/gout (NCT02246673, NCT02317861) and one study in healthy volunteers (NCT01883167). Subjects were administered febuxostat oral doses from 10 to 80mg. The pharmacokinetics of febuxostat was analyzed using non-linear mixed-effects modeling as implemented in NONMEM 7.3.0. The dataset consisted of racially diverse subjects, 40% being Japanese, 10% of unknown Asian origin, 39% Caucasian, and 10% Black. Most subjects (n = 92, 63%) had normal creatinine clearance (90mL/min), while 52 subjects (36%) had mild renal impairment (creatinine clearance > 60 to < 90) at baseline. The effect of disease state, body weight, and creatinine clearance on febuxostat pharmacokinetics was investigated using stepwise covariate modeling. Febuxostat pharmacokinetics was well described by a two-compartment disposition model. Asian race was the only covariate resulting in a potentially clinically important increase in febuxostat area under the curve (1.64-fold, 90% confidence interval 1.48-1.79) compared with Caucasian individuals. The difference in body weight between Asian and Caucasian subjects did not explain the difference in febuxostat exposure. Absorption was modeled as a sequential zero- to first-order process with lag-time. In this pooled analysis of three studies, we show that Asian individuals have a 1.64-fold higher febuxostat exposure than Caucasians, independent of bodyweight or other investigated covariates.These findings may be of importance when selecting starting febuxostat doses in Asian patients.

Impact of vitaminD receptor gene polymorphisms on vitiligo susceptibility and clinical features inaSoutheastern European Caucasian population.

An association of vitamin D receptor (VDR) polymorphisms and vitiligo has been suggested. However, previous studies have reported contradictory results while including limited data among Caucasians. The aim of this single-center study was to evaluate the effect of three common VDR gene polymorphisms (FokI, TaqI and BsmI) on suscep-tibility and clinical aspects of vitiligo in a Southeastern European Caucasian population. A total of 110 unrelated vitiligo cases and 509 general population controls were enrolled from October 2018 to November 2019. Genomic DNA was extracted from whole blood after de-identification and anonymization of the samples and genotyped for the selected VDR polymorphisms by the qPCR (melting curve analysis). Subgroup analysis by clinical features among subsets of patients indicated that, compared to subjects with the FokI TT genotype or T allele, carriers of the FokI CC genotype or C allele exhibited significantly decreased risk of developing vitiligo before the age of 30 [TT vs. CC: odds ratio (OR)=0.286, 95% confidence interval (CI): 0.083-0.984, P=0.041; T vs. C: OR=0.545, 95% CI: 0.313-0.948, P=0.031]. Intra-patient analysis also revealed that, compared to T allele, the presence of TaqI C allele was adversely associated with the incidence of concurrent leukotrichia (T vs. C: OR=1.874, 95% CI: 1.018-3.451, P=0.042). Comparisons between the case and control groups showed no evidence to support an association between susceptibility to vitiligo and the VDR BsmI, TaqI, and FokI polymorphisms in this cohort. Thus, the studied VDR polymorphisms might indirectly impact the clinical course and treatment decision-making despite their lack of association with vitiligo per se. Further research with larger sample sizes, especially across Caucasian individuals, should be performed to confirm these findings.

An odontometric study of tooth dimension in diastematic dentition.

One of the causes of the maxillary midline diastema (MMD) may be discrepancy between teeth and maxilla dimension. That can relate to two situations: when teeth have correct size but maxilla is too large or maxilla bone is in the proper size but teeth have reduced dimensions (microdontia). The present study has been conducted to investigate the differences in the linear dimensions of upper central and lateral incisors and canines in diastematic dentition and to compare them with the control group without diastema. The study was conducted on Caucasian individuals (n = 102) divided into two groups: study group with MMD (n = 50) and control group without MMD (n = 52). The following measurements were done by digital calliper on their plaster models: 1. Width in the widest mesiodistal portion for upper right and left central incisors, lateral incisors and canines. 2. Length in the longest apico-coronal portion for the same teeth. Statistical analysis showed that comparisons of widths of left canines were significant. In the study group widths of left canines were lower than in the control group. Statistically significant differences in the length were observed for central incisors and canines in both sides. All measurements were lower in the diastema group of patients. Patients with diastema were characterised by incorrect tooth dimensions. The central incisors and upper canines were shorter in this group. Aesthetic closing of the diastema requires not only widening the crowns of the front teeth but also their elongation.

Recurrent Rare Copy Number Variants Increase Risk for Esotropia.

PurposeTo determine whether rare copy number variants (CNVs) increase risk for comitant esotropia.MethodsCNVs were identified in 1614 Caucasian individuals with comitant esotropia and 3922 Caucasian controls from Illumina SNP genotyping using two Hidden Markov model (HMM) algorithms, PennCNV and QuantiSNP, which call CNVs based on logR ratio and B allele frequency. Deletions and duplications greater than 10 kb were included. Common CNVs were excluded. Association testing was performed with 1 million permutations in PLINK. Significant CNVs were confirmed with digital droplet polymerase chain reaction (ddPCR). Whole genome sequencing was performed to determine insertion location and breakpoints.ResultsEsotropia patients have similar rates and proportions of CNVs compared with controls but greater total length and average size of both deletions and duplications. Three recurrent rare duplications significantly (P = 1 × 10−6) increase the risk of esotropia: chromosome 2p11.2 (hg19, 2:87428677-87965359), spanning one long noncoding RNA (lncRNA) and two microRNAs (OR 14.16; 95% confidence interval [CI] 5.4–38.1); chromosome 4p15.2 (hg19, 4:25554332-25577184), spanning one lncRNA (OR 11.1; 95% CI 4.6–25.2); chromosome 10q11.22 (hg19, 10:47049547-47703870) spanning seven protein-coding genes, one lncRNA, and four pseudogenes (OR 8.96; 95% CI 5.4–14.9). Overall, 114 cases (7%) and only 28 controls (0.7%) had one of the three rare duplications. No case nor control had more than one of these three duplications.ConclusionsRare CNVs are a source of genetic variation that contribute to the genetic risk for comitant esotropia, which is likely polygenic. Future research into the functional consequences of these recurrent duplications may shed light on the pathophysiology of esotropia.

HLA-B*40:462 was likely generated by a recombination event between B*40:01:02 and B*13:02:01.

The new B*40:462 allele was characterized in a Caucasian Spanish individual.

Expanding the phenotypic spectrum consequent upon de novo WDR37 missense variants.

Structural eye disorders are increasingly recognised as having a genetic basis, although current genetic testing is limited in its success. De novo missense variants in WDR37 are a recently described cause of a multisystemic syndromic disorder featuring ocular coloboma. This study characterises the phenotypic spectrum of this disorder and reports 2 de novo heterozygous variants (p.Thr115Ile, p.Ser119Tyr) in three unrelated Caucasian individuals. All had a clinical phenotype consisting of bilateral iris and retinal coloboma, developmental delay and additional, variable multisystem features. The variants fall within a highly conserved region upstream of the WD-repeat domains, within an apparent mutation cluster. Consistent with the literature, intellectual disability, structural eye disorders, epilepsy, congenital heart disease, genitorenal anomalies and dysmorphic facial features were observed. In addition, a broader developmental profile is reported with a more specific musculoskeletal phenotype described in association with the novel variant (p.Thr115Ile). We further expand the phenotypic spectrum of WDR37-related disorders to include those with milder developmental delay and strengthen the association of ocular coloboma and musculoskeletal features. We promote the inclusion of WDR37 on gene panels for intellectual disability, epilepsy and structural eye disorders.

Factors Predicting Participation in the Prospective Genomic Sequencing Study, Total Cancer Care (TCC), in Kentucky.

Large-scale genomic sequencing studies are driving oncology drug development. However, rural populations, like those residing in Appalachian Kentucky, are underrepresented in these efforts. In this study, we determined the frequency of participation, reasons for nonparticipation, and factors predicting the decision to participate in the Total Cancer Care (TCC) prospective genomic cohort study. A total of 1,188 patients were invited to enroll in the TCC prospective cohort from December 2018 to May 2019. Declining patients were queried for their rationale for nonparticipation and their patient data were obtained from the Kentucky Cancer Registry (KCR). Logistic regression was used to assess the association between characteristics and study participation. The association of study participation with survival was modeled with Cox proportional-hazards regression. 90.9% (1,081) patients consented to participate. In multivariate analysis, factors significantly associated with participation were age, gender, treatment status, and race. Though overall more women participated in the study, men were more likely to participate than women when invited (OR 1.57). Younger, Caucasian individuals who had received chemotherapy, but not surgery, were also more likely to participate. Patients in the Kentucky Appalachian cohort were primarily rural, had less educational attainment, and lower socioeconomic status. Kentucky Appalachian patients were no less likely to enroll in TCC than non-Appalachian patients. Consented individuals had higher overall survival compared to those who declined. Though minorities, those with low socioeconomic status, and rural populations are underrepresented in genomic studies, they were no less likely to participate when given the opportunity, and participation was associated with better clinical outcomes.

A Comparative Study on Loadings of the Lower Extremity during Deep Squat in Asian and Caucasian Individuals via OpenSim Musculoskeletal Modelling

Populations of different ethnicities may present different movement capacities and muscular function adaptations. The purpose of this study was to investigate the differences of motion and loading in the lower extremity during dynamic deep squats between Asian and Caucasian individuals using OpenSim modelling technique with a customized squat-specific musculoskeletal model. Twenty-four participants joined the test performing the step-squat test, with right foot stepping side, squatting, and returning. The one-dimensional statistical parametric mapping package was used for statistical analysis. The main findings of the current study were as follows: (1) significant lower squat depth was observed in the Asian individuals, (2) the greater knee range of motion and contact forces were found in the Asian individuals, and (3) the greater ankle contact forces in the Caucasian individuals were notable while performing the deep squat compared to the Asian group. Knowledge found in the current study may provide implication for exercise practitioners and physiotherapists while designing schemes for the prevention of loading accumulation in the lower extremity.

Race and cultural factors in an RCT of prolonged exposure and sertraline for PTSD

The efficacy of treatments for posttraumatic stress disorder (PTSD) among African Americans is less clear given underrepresentation in clinical research. Additionally, intervention research examining race has typically not considered within-group heterogeneity, such as acculturation, ethnic identity, and cultural attitudes. In a randomized controlled trial, African American (n = 43) and Caucasian (n = 130) individuals received prolonged exposure (PE) or sertraline for PTSD, comparing: treatment response, retention, and treatment beliefs and preferences. Indirect effects of cultural variables were also examined. African Americans reported stronger ethnic identity (d = 0.71), less positive attitudes toward other groups (d = 0.36), and less acculturation (d = 0.51) than Caucasians. Noninferiority analyses indicated clinically equivalent PTSD outcomes for African Americans and Caucasians in both treatments. Groups showed comparable improvements in depression and functioning, and similar treatment preferences and beliefs. African Americans attended fewer sessions in PE (d = 0.87) and sertraline (d = 0.53) than Caucasians. Indirect effects analyses indicated positive cultural attitudes toward other ethnoracial groups were consistently associated with better treatment outcome and retention. Despite no differential effectiveness, findings may highlight the need to target retention among African Americans. Within-group cultural aspects of race may be an informative complement to basic, categorical conceptualizations.

Importance of standardizing the number of cells measured for coefficient of variation (COV) estimates of corneal endothelial cell area values as relevant to contact lens wear

PurposeTo assess the impact of using different numbers of cells in calculations of the coefficient of variation (COV) value for normal and polymegethous endothelia MethodsFour sets of 20 non-contact specular microscope images obtained from Caucasian individuals were assessed, and categorized according to the extent of polymegethism, i.e. grade 0 (none), grade 1 (mild), grade 2 (moderate) and grade 3 (substantial). Cell areas were measured manually and then values for between 2 and 100 cells were progressively added and averaged to generate COV estimates. These were then assessed in terms of their relative values (as percentages +/- SD) in relation to the value obtained on over 100 cells. ResultsFor the 4 sets of endothelia with group-mean COV values of 25.8, 33.1, 45.1 and 56.8%, the reliability of the COV estimates realized asymptotic values of close to ±1.0, ±2.7, ±3.6 and ±5.0% with 90 cells, but with greater uncertainty with few numbers of cells, e.g. only to within ±3.4, ±5.3, ±6.1 and ±7.9% with 75 cells. ConclusionsCOV estimates for the corneal endothelium are dependent on the number of cells used in the calculations. It is recommended that every effort should be made to not only assess 75–100 cells per endothelial image, but that this number should be the same or very similar for all endothelial images in a particular data set so that the uncertainly (or estimated proportional error) in the estimates is balanced.

Abstract IA06: Understanding the molecular landscape of gastric premalignant lesions

Abstract Even though the incidence of gastric cancer has been declining over the years, it still has a very high mortality rate. The incidence and mortality of gastric cancer is, however, significantly higher in minority populations with African Americans and Hispanic individuals presenting 52% and 43%, respectively, more cases than Caucasians (data for male patients). Gastric adenocarcinoma has been strongly associated to infection with Helicobacter pylori (H. pylori). The infection triggers an inflammatory cascade, known as the Correa's cascade, that changes the normal gastric epithelium into nonatrophic gastritis (NAG), multifocal atrophic gastritis (MAG), intestinal metaplasia (IM), dysplasia, and cancer. It is known that these events involve immune infiltration and damage to the gastric mucosa; however, there is still too much to learn about the gastric premalignant stages and the evolution of them over time. Over the years we have identified single-nucleotide polymorphisms (SNPs) and differential expression of genes associated with premalignant stages and with evolution of the disease over time. We found that African Americans have increased incidence of advanced premalignant lesions and have more prevalence of infection with H. pylori than Whites. In addition, we found that SNPs and haplotypes in the interleukin 1 b gene (IL1B) are associated with advanced gastritis in African American individuals. Interestingly, the frequency of these inflammatory SNPs and haplotypes is different among African American and Caucasian individuals. In terms of gene expression, we have also found that the increased expression of the gene deleted in malignant brain tumors 1 (DMBT1) is associated with the development of advanced gastritis while the expression of CD44 is associated with progression of the disease over time. Given that CD44 is a molecule involved in the homing of inflammatory cells, its association with progression of premalignant stages over time highlights the role of the immune response in the outcome of these lesions. Interestingly, these immune responses seem to be also modulated by H. pylori itself. We have shown that H. pylori components are able to modulate acquired and innate immune responses. In addition, we have also found a microRNA pattern associated with advanced premalignant gastric lesions in both African Americans and Caucasians. Understanding the molecular landscape of the gastric lesions may help us devise strategies to intervene and limit their progression into more advanced lesions, including gastric cancer. Citation Format: Jone Garai, Maria B. Piazuelo, Maria C. Camargo, Pelayo Correa, Keith Wilson, Jovanny Zabaleta. Understanding the molecular landscape of gastric premalignant lesions [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr IA06.

Outcome in Caucasian patients with hepatitis B e antigen negative chronic infection: A long-term observational cohort study.

Sensitive polymerase chain reaction assays to measure hepatitis B virus (HBV) DNA became only available the last decade. Hence, the long‐term outcome of Caucasian patients in Western Europe with hepatitis B e antigen (HBeAg)‐negative chronic infection, especially with a baseline HBV DNA level ⩾2000 IU/mL, is still unclear. Out of a cohort of 1936 chronic HBV patients, 413 Caucasian individuals were identified with HBeAg‐negative chronic infection, defined as persistently normal alanine aminotransferase (ALT) levels and HBV DNA levels <20 000 IU/mL. During a mean follow‐up of 12 years, 366 (88.6%) maintained an HBeAg‐negative chronic infection status, whereas 25 (6.1%) developed chronic active hepatitis (CAH). In total, Nine of these 25 CAH cases were related to immunosuppression. In total, 22 (5.3%) individuals had ALT > 2 × upper limit of normal due to non‐HBV‐related causes. The cumulative probability of spontaneously developing CAH after 10 years was almost exclusively seen in patients with baseline HBV DNA level ⩾2000 IU/mL (11.7% vs 1.2%; P < .001). Advanced liver disease developed significantly more in patients with baseline HBV DNA level ⩾2000 IU/mL (5.2% vs 1.5%; P = .018) and occurred especially in patients with obesity (16.7% vs 4.2%; P = .049). The incidence of hepatocellular carcinoma was 0.0%. Caucasian patients with HBeAg‐negative chronic infection and baseline HBV DNA level <2000 IU/mL have an excellent long‐term prognosis in the absence of immunosuppressive therapy. However, patients with baseline HBV DNA level ⩾2000 IU/mL are at risk to develop advanced liver disease.

Systemic Redox Imbalance in Patients with Chronic Granulomatous Disease.

The aim of our study was to evaluate redox status, enzymatic and non-enzymatic antioxidant barriers, oxidative damage of proteins, lipids and DNA, as well as concentration of coenzyme Q10 and vitamins A and E in patients with chronic granulomatous disease (CGD). The study was performed on fifteen Caucasian individuals (median age 24 years and seven months) diagnosed with CGD. The mutation in the NCF1 gene was confirmed in ten patients, and in the CYBB gene in five patients. We demonstrated high levels of total oxidant status (TOS) and oxidative stress index (OSI), lipids (↑8-isoprostanes (8-isoP), ↑4-hydroxynonenal (4-HNE)), proteins (↑advanced oxidation protein products (AOPP)) and DNA (↑8-hydroxy-2’-deoxyguanosine (8-OHdG)) oxidation products in CGD individuals as compared to sex- and age-matched healthy controls. We showed enhanced serum enzymatic activity of catalase (CAT) and superoxide dismutase-1 (SOD) and significantly decreased coenzyme Q10 concentration. Our study confirmed redox disturbances and increased oxidative damage in CGD patients, and indicated the need to compare redox imbalance depending on the type of mutation and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity. The question regarding effectiveness of antioxidant therapy in patients with CGD is open, and the need to establish guidelines in this area remains to be addressed.

In Search of Normality for Vitamin K1: Establishing Age-Dependent Reference Intervals in the Danish Population.

A growing body of evidence suggests that vitamin K has beneficial effects on human health, especially cardiovascular and bone health. Vitamin K1 (phylloquinone), the predominant form of vitamin K in blood, is regarded as an indicator of vitamin K status, but to our knowledge no reference intervals (RIs) have been established for vitamin K1. In this population-based study, vitamin K1 was measured in serum from 3808 Caucasian individuals without diabetes from 26 to 78 years of age. The need for gender- and age-partitioned vitamin K1 reference intervals was evaluated using Lahti's method, and exclusion criteria were defined to obtain as healthy a study group as possible. The excluded subgroups were tested for differences in mean serum vitamin K1 levels. Serum vitamin K1 levels were quantified using an in-house newly developed, validated, and highly sensitive online SPE-LC-MS/MS method with a limit of quantitation of (LOQ) 0.05 nmol/L. The reference interval for serum vitamin K1 was 0.22 to 3.95 nmol/L for individuals aged 26 to 44 years and 0.35 to 3.70 nmol/L for individuals aged 45 to 78. Similar age-specific reference intervals were established for vitamin K1-triglyceride ratio being 0.20 to 3.16 and 0.31 to 3.44, respectively. No significant difference was found between genders. Serum vitamin K1 was detectable in all serum samples. Individuals with known comorbidity were found to have significantly lower serum vitamin K1 compared to those without comorbidity. Current smokers had lower serum vitamin K1 compared to nonsmokers. Age-dependent reference intervals were established for serum vitamin K1 and vitamin K1-triglyceride ratio in a well-defined, healthy Caucasian population. Lower serum vitamin K1 levels were found in individuals with known comorbidity, suggesting an association between serum vitamin K1 and disease status. Further studies are needed to determine an optimal serum vitamin K1 level.

Comparison of the Morphology of the Foveal Pit Between African and Caucasian Populations.

PurposeThe purpose of this study was to characterize foveal pit morphology in an African (Ghanaian) population, to compare it to that of a Caucasian group and to determine if it varied with age in the two populations.MethodsThe depth, diameter, slope, and volume of the foveal pit were interpolated from optical coherence tomography volume scans recorded in 84 Ghanaian and 37 Caucasian individuals. Their association with age, sex, and ethnicity was investigated using multilevel regression models.ResultsThe foveal pit differed significantly in width, slope, and volume between Ghanaian men and women (P < 0.001), but only in width and volume between Caucasian men and women (P < 0.01). In Ghanaians, age was associated with a narrowing of the foveal depression and a reduction of its volume. Overall, these changes were more pronounced in women as compared to men and were largely absent from the Caucasian group. When controlled for age, the foveal pit of Ghanaians was significantly wider and larger in volume as compared to the Caucasian group (P < 0.001).ConclusionsThe morphology of the foveal pit differs between African and Caucasian individuals. These anatomic differences should be considered when examining differences in prevalence and clinical features of vitreoretinal disorders involving the fovea between the two populations.Translational RelevanceDifferences in retinal anatomy may partly explain variations in the prevalence and clinical features of retinal diseases between Africans and Caucasians. Such differences should be adequately considered in diagnoses and monitoring of ocular diseases in patients with African ancestry.

Subordinate Effect of -21M HLA-B Dimorphism on NK Cell Repertoire Diversity and Function in HIV-1 Infected Individuals of African Origin.

Natural Killer (NK) cells play an important role in antiviral defense and their potent effector function identifies them as key candidates for immunotherapeutic interventions in chronic viral infections. Their remarkable functional agility is achieved by virtue of a wide array of germline-encoded inhibitory and activating receptors ensuring a self-tolerant and tunable repertoire. NK cell diversity is generated by a combination of factors including genetic determinants and infections/environmental factors, which together shape the NK cell pool and functional potential. Recently a genetic polymorphism at position -21 of HLA-B, which influences the supply of HLA-E binding peptides and availability of HLA-E for recognition by the inhibitory NK cell receptor NKG2A, was shown to have a marked influence on NK cell functionality in healthy human cytomegalovirus (HCMV) seronegative Caucasian individuals. In this study, -21 methionine (M)-expressing alleles supplying HLA-E binding peptides were largely poor ligands for inhibitory killer immunoglobulin-like receptors (KIRs), and a bias to NKG2A-mediated education of functionally-potent NK cells was observed. Here, we investigated the effect of this polymorphism on the phenotype and functional capacity of peripheral blood NK cells in a cohort of 36 African individuals with human immunodeficiency virus type 1 (HIV-1)/HCMV co-infection. A similarly profound influence of dimorphism at position -21 of HLA-B on NK cells was not evident in these subjects. They predominantly expressed African specific HLA-B and -C alleles that contribute a distinct supply of NKG2A and KIR ligands, and these genetic differences were compounded by the marked effect of HIV-1/HCMV co-infection on NK cell differentiation. Together, these factors resulted in a lack of correlation of the HLA-B -21 polymorphism with surface abundance of HLA-E and loss of the NK cell functional advantage in subjects with -21M HLA-B alleles. Instead, our data suggest that during HIV/HCMV co-infection exposure of NK cells to an environment that displays altered HLA-E ligands drives adaptive NKG2C+ NK cell expansions influencing effector responses. Increased efforts to understand how NK cells are functionally calibrated to self-HLA during chronic viral infections will pave the way to developing targeted therapeutic interventions to overcome the current barriers to enhancing immune-based antiviral control.