Metabolic syndrome is associated with higher rates of cardiovascular morbidity and mortality. Although significant disparities in the risks of metabolic syndrome by occupation type and sex are well ...documented, the factors associated with metabolic syndrome in low‐ to middle‐income countries remain unclear. These gaps in evidence identify the need for patterns of metabolic syndrome among hospital personnel of both sexes in Nigeria. A total of 256 hospital workers comprising 32.8% men were studied. The mean age of the participants was 42.03±9.4 years. Using International Diabetic Federation criteria, the prevalence of metabolic syndrome was 24.2%. Women were substantially and significantly more likely to be identified with metabolic syndrome compared with men (34.9% vs 2.4%, respectively; P=.0001). This study identified metabolic syndrome among health workers with over one third of women with metabolic syndrome compared with <10% of men. These results support the implementation of lifestyle modification programs for management of metabolic syndrome in the health care workplace.
Background: Excess cardiovascular burden in patients with chronic kidney disease (CKD) has been attributed to the occurrence of CKD–Mineral Bone Disease (CKD – MBD). This study aimed to determine the ...spectrum of CKD-MBD among Nigerians with CKD using Fibroblast Growth Factor 23 (FGF 23) and intact Parathyroid Hormone (iPTH).
Methods: Cross sectional survey of 105 patients with non-diabetic CKD and 104 controls. Information obtained were demographics, aetiology of CKD, features of CKD-MBD. Serum iPTH and FGF 23 were assayed.
Results: The mean ages were 48.7±15.3 vs 48.6±17.4 years while 54.7% and 45.2% were males for cases and controls, respectively. The mean plasma FGF 23 (392.8±35.3 vs 133.8±22.7 RU/mL and plasma iPTH (289±25.6 vs 118±10.8 ng/L, respectively. The frequency of elevated FGF 23 (45.7% vs 24.0%, p<0.01) and abnormal iPTH (53.3% vs 14.1%, p- 0.01) were higher in cases. The prevalence of MBD were (59.0% vs 14.4%, p<0.01) in cases and controls while dialysis status OR 2.94, 95% CI (1.2803–5.3645), and elevated FGF 23 OR, 1.87, 95% CI (1.1782–5.4291) were associated with CKD-MBD.
Conclusion: The study demonstrated high prevalence of CKD-MBD among patients with non-diabetic CKD while FGF23 and iPTH were useful assays in the diagnosis of CKD-MBD among Nigerians with CKD.
Keywords: CKD; mineral bone disease; diagnostic; FGF 23; parathyroid hormone.
Recurrence of hepatitis C, the main indication for liver transplantation in the United States, leads to rapid fibrosis progression and worse outcomes compared to other indications. While clinical ...variables play a role, they are insufficient to explain all inter-patient variability in posttransplant fibrosis progression. Genetic factors associated with hepatitis C virus (HCV) outcomes have been identified, but limited studies have been conducted in the context of HCV-related liver transplantation. Therefore, the purpose of this study was to examine candidate genes related to the immune response and rate of fibrosis in subjects undergoing liver transplantation for HCV.
One hundred twelve recipients with detailed posttransplant fibrosis and clinical information were genotyped using 25 single nucleotide variants (SNVs), including five SNVs within the IL28B gene region. Associations between SNVs and rapid fibrosis progression were performed controlling for pertinent clinical variables and haplotype analyses for the IL28B gene were completed.
Significant multivariable associations were found for rs8099917 (IL28B), rs1991401 (DDX5), rs4969168 (SOC3), and rs7976497 (MLEC). The minor allele was protective against rapid fibrosis progression for the IL28B SNV (G allele), MLEC SNV (T allele), and DDX5 SNV (G allele). For the SOC3 SNV, the minor allele (A) increased the risk for rapid fibrosis progression. Additionally, two recipient haplotype structures for IL28B were significantly associated with rapid fibrosis progression.
These findings indicate that recipient genetic factors play a role in posttransplant HCV-related fibrosis progression. Molecular studies of these pathways may elucidate the pathogenesis of posttransplant fibrosis progression and provide risk prediction markers.
The doubly labeled water (DLW) method is used to measure free-living energy expenditure in humans. Inherent to this technique is the assumption that natural abundances of stable isotopes (2)H and ...(18)O in body water remain constant over the course of the measurement period and after elimination of the loading dose of DLW will return to the same predose level. To determine variability in the natural abundances of (2)H and (18)O in humans living in a region with seasonal shifts in rain patterns and sources of drinking water, over the course of 12 mo we collected weekly urine samples from four individuals living in southwest Nigeria as well as samples of their drinking water. From ongoing regional studies of hypertension, obesity, and energy expenditure, we estimated average water turnover rate, urine volumes, and sodium and potassium excretion. Results suggest that (2)H and (18)O in urine, mean concentrations of urinary sodium and potassium, urine volume, and total body turnover differed significantly from dry to rainy season. Additionally, seasonal weather variables (mean monthly maximum temperatures, total monthly rainfall, and minimum relative humidity) were all significantly associated with natural abundances in urine. No seasonal difference was observed in drinking water samples. Findings suggest that natural abundances in urine may not remain constant as assumed, and studies incorporating DLW measurements across the transition of seasons should interpret results with caution unless appropriate doses of the tracers are used.
Familial component is estimated to account for about 10% of ovarian cancer. However, the mode of inheritance of ovarian cancer remains poorly understood. The goal of this study was to investigate the ...inheritance model that best fits the observed transmission pattern of ovarian cancer among 7669 members of 1919 pedigrees ascertained through probands from the Gilda Radner Familial Ovarian Cancer Registry at Roswell Park Cancer Institute, Buffalo, New York.
Using the Statistical Analysis for Genetic Epidemiology program, we carried out complex segregation analyses of ovarian cancer affection status by fitting different genetic hypothesis-based regressive multivariate logistic models. We evaluated the likelihood of sporadic, major gene, environmental, general, and six types of Mendelian models. Under each hypothesized model, we also estimated the susceptibility allele frequency, transmission probabilities for the susceptibility allele, baseline susceptibility and estimates of familial association. Comparisons between models were carried out using either maximum likelihood ratio test in the case of hierarchical models, or Akaike information criterion for non-nested models. When assessed against sporadic model without familial association, the model with both parent-offspring and sib-sib residual association could not be rejected. Likewise, the Mendelian dominant model that included familial residual association provided the best-fitting for the inheritance of ovarian cancer. The estimated disease allele frequency in the dominant model was 0.21.
This report provides support for a genetic role in susceptibility to ovarian cancer with a major autosomal dominant component. This model does not preclude the possibility of polygenic inheritance of combined effects of multiple low penetrance susceptibility alleles segregating dominantly.
Whereas genome-wide association study (GWAS) has proven to be an important tool for discovery of variants influencing many human diseases and traits, unfortunately its performance has not been much ...of all-around success for some complex conditions, for example, hypertension. Because some of the existing effective pharmacotherapeutic agents act by targeting known biological pathways, pathway-based analytical approaches could lead to more success in discovery of disease-associated variants. The objective of the present study was to identify functional variants associated with blood pressure in the aldosterone-regulated sodium reabsorption pathway using the simulated and real blood pressure phenotypes provided for Genetic Analysis Workshop 19.
The present analysis included 1942 samples with exome sequencing data and for whom blood pressure phenotypes were available. Because only odd-numbered autosomes were available, we restricted analysis to 127 quality-controlled single-nucleotide polymorphisms from the aldosterone-regulated sodium reabsorption pathway. We performed pathway-based association analysis using appropriate regression models for single variant, haplotype and epistasis association analyses. To account for multiple comparisons, statistical significance was empirically derived by permutation procedure and Bonferroni correction.
The topmost pathway-based association signals were observed in
gene for diastolic blood pressure (DBP), systolic blood pressure (SBP), and mean arterial pressure (MAP) in both real and simulated data. The associations remained significant (
<0.05) after multiple testing corrections for the number of genes. Similarly, the pathway-based 2-locus epistasis analysis indicated significant interactions between
and
for SBP and MAP;
and
for DBP;
and
for hypertension in the real data set. We also observed significant within-gene interactions in
for SBP, DBP, and hypertension in the simulated data set.
The findings from this study show that pathway-based analytical approach targeting known biological pathways can be useful in identification of disease-associated variants that are otherwise undetectable by GWAS. The approach takes advantage of the assumption of nonindependence of variants within and across pathway genes which leads to reduced penalty of multiple testing and thus less-stringent statistical significance threshold.
Elevated blood pressure (BP) shares a level of heritability similar to many other traits related to cardiovascular risk; however, specific susceptibility loci have been difficult to localize. We ...conducted a multistage study of BP as a continuous trait in a low-risk West African population in which it was anticipated that environmental exposures would be reduced in complexity and intensity. In our earlier genome-wide linkage study for BP in this population, strong linkage evidence was noted on chromosomes 6 and 7.
We subsequently genotyped a total of 3431 tag single-nucleotide polymorphisms (SNPs) in 3 regions (viz, 152.68 to 165.99 Mb on chromosome 6, 0.29 to 20.67 Mb, and 104.09 to 123.06 Mb on chromosome 7) in 713 individuals from 199 families. We conducted a family-based association analysis using individual SNPs and associated haplotypes. After correction for multiple comparisons, 6 intronic and 1 intergenic SNPs achieved nominal statistical significance (P<0.05) for the association with BP. The associated intronic SNPs include 2 in the PARK2 gene on chromosome 6; 2 in the KCND2 gene, and 1 each in the C7orf58 and HDAC9 genes on chromosome 7. The intergenic SNP is located between the RPA3 and GLCCI1 genes on chromosome 7. The haplotypes on which these SNPs resided were more strongly associated with BP than their respective single SNPs. The frequency of the "at-risk" haplotypes ranged from 14% to 48%.
These data provide preliminary evidence that regions on chromosomes 6 and 7 may influence susceptibility to elevations in BP.
Objective: Obesity is a prevalent condition in industrialized societies and is increasing around the world. We sought to assess the relative importance of resting energy expenditure (REE) and ...activity EE (AEE) in two populations with different rates of obesity.
Methods and Procedures: Women of African descent between 18 and 59 years of age were recruited from rural Nigeria and from metropolitan Chicago. Total EE (TEE) was measured using the doubly labeled water (DLW) technique and REE by indirect calorimetry; AEE was calculated as the difference between TEE and the sum of REE plus a factor for the thermic effect of food. In the analyses all EE parameters were adjusted for body size using a regression method. Comparisons were made between the groups and associations between EE and adiposity examined.
Results: A total of 149 Nigerian and 172 African‐American women completed the protocol. All body size measurements were lower in the Nigerian women. Adjusted TEE and REE were higher in the Nigerian cohort but adjusted AEE did not differ significantly. Adjustment for parity, seasonality, and recent illness did not modify mean AEE or adiposity. In neither cohort was there a meaningful association between measures of AEE and adiposity.
Discussion: In these cohorts of women from very different environments, AEE did not differ significantly nor was it associated cross‐sectionally with adiposity. If generalizable, these findings suggest that reduction in AEE may have less of a role in the development of obesity than anticipated. The possibility remains that variation in type and duration of activity plays a role not captured by total AEE.
α-Thalassemia and the BCL11A rs1427407 T allele are commonly observed in sickle cell anemia (SCA) patients and are associated with reduced hemolysis and higher hemoglobin F levels, respectively. We ...investigated whether a high-risk genetic profile, defined as SCA patients who did not inherit either α-thalassemia or the BCL11A rs1427407 T allele, had stronger associations with clinical and laboratory variables than the individual genetic components in the University of Ibadan cohort (N = 249). We then replicated our findings in SCA cohorts from the University of Illinois at Chicago (UIC) (N = 260) and the Walk-Treatment of Pulmonary Hypertension and Sickle Cell Disease with Sildenafil Therapy study (Walk-PHaSST) (N = 387). A high-risk genetic profile was associated with higher reticulocytes (15.0% vs 7.8%, P = .08) and stroke history (6% vs 1%, P = .02) than standard-risk patients, and these associations were more significant than the individual genetic components in the University of Ibadan cohort. These findings were replicated in high-risk patients from UIC and Walk-PHaSST for reticulocytes (UIC: 13.5% vs 11.8%, P = .03; Walk-PHaSST: 9.6% vs 8.2%, P = .0003) and stroke history (UIC: 32% vs 22%, P = .07; Walk-PHaSST: 14% vs 7%, P = .01). On combined analysis, a high-risk genetic profile had strong associations with increased markers of hemolysis (hemoglobin β = –0.29, 95% confidence interval CI: −0.50 to −0.09; P=.006; reticulocyte% β = 2.29, 95% CI: 1.31-3.25; P = 1 × 10−5) and stroke history (odds ratio = 2.0, 95% CI: 1.3-3.0; P = .0002), but no association with frequent vaso-occlusive crises (≥3 per year). A high-risk genetic profile is associated with increased hemolysis and stroke history in 3 independent cohorts. This profile may help identify patients to prioritize for hydroxyurea and for closer monitoring strategies for stroke.
•A genetic risk profile integrating α-thalassemia and BCL11A status improves associations with hemolytic markers and stroke history.
The hepatitis C virus (HCV), which was not recognized as an infectious agent until the 1980s, is responsible for a worldwide epidemic. The World Health Organization estimates global prevalence at ...2.8%, with 185 million persons infected. In contrast to hepatitis B, where successful vaccine campaigns have reduced the disease burden, much less progress has been made toward the control of HCV. Phylogenetic studies suggest that HCV originated in Africa and has been endemic in some regions for at least 500–600 years. However, little is known about the epidemiology, transmission, and clinical course of HCV in Africa. With the advent of highly effective anti-HCV agents, there exists great potential to at least curb the global epidemic. For regions such as sub-Saharan Africa, however, this will require a thorough understanding of the regional population-level epidemiology, risk factors, and transmission mechanisms. Only then can effective treatment and prevention strategies be introduced.
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