Hyperinsulinemia, Insulin Resistance, Vitamin D, and Colorectal Cancer Among Whites and African Americans

African Americans have the highest incidence and mortality rates of colorectal cancer among all US racial and ethnic groups. Dietary factors, lifestyle factors, obesity, variability in screening rates, socioeconomic differences, barriers to screening, and differences in access to health care may be contributory factors to racial and ethnic disparities. African Americans are more likely to demonstrate microsatellite instability in their colorectal tumors leading to malignancy. However, these differences do not completely explain all the variances. Ample evidence implicates insulin resistance and its associated conditions, including elevated insulin and insulin-like growth factor-1 (IGF-1), in colorectal carcinogenesis. African Americans have a high risk for and a high prevalence of insulin resistance and subsequent overt type 2 diabetes. Recent clinical studies revealed that ethnic differences between whites and African Americans in early diabetes-related conditions including hyperinsulinemia already exist during childhood. African Americans have a much higher prevalence of vitamin D deficiency than whites throughout their life spans. Vitamin D deficiency has been associated with higher rates of diabetes and colorectal cancer, particularly in individuals with high serum insulin and IGF-1 levels. Moreover, African Americans have lower insulin sensitivity in tissues, independent of obesity, fat distribution, and inflammation. Further development of measures of biomarkers of tumor biology and host susceptibility may provide further insight on risk stratification in African Americans.     

IL4R alpha mutations are associated with asthma exacerbations and mast cell/IgE expression

BACKGROUND: Severe asthma has been associated with severe exacerbations, lower lung function and greater tissue inflammation. Previous studies have suggested that mutations in interleukin-4 receptor alpha (IL4Ralpha) are associated with lower lung function, higher IgE, and a gain in receptor function. However, an effect on exacerbations and tissue inflammation has not been shown. HYPOTHESIS: Allelic substitutions in IL4Ralpha are associated with asthma exacerbations, lower lung function, and tissue inflammation, in particular to mast cells and IgE. METHODS: Two well-characterized cohorts of subjects with severe asthma were analyzed for five single nucleotide polymorphisms (SNPs) in IL4Ralpha. These polymorphisms were compared with the history of severe asthma exacerbations and lung function. In the primary (National Jewish) cohort, these polymorphisms were also compared with endobronchial tissue inflammatory cells and local IgE. RESULTS: In both cohorts, the presence of the minor alleles at E375A and Q551R, which were more common in African Americans, was associated with a history of severe exacerbations and lower lung function. In the National Jewish cohort, the C allele at E375A was associated with higher tissue mast cells and higher levels of IgE bound to mast cells. The significance for most of these associations remained when whites (the larger racial subgroup) were analyzed separately. CONCLUSIONS: SNPs in IL4Ralpha, which are more common in African Americans, are associated with severe asthma exacerbations, lower lung function, and increased mast cell-related tissue inflammation. Further studies of the impact of these mutations in African Americans and on receptor function are indicated.     

大动脉粥样硬化性卒中与脑小血管病患者血小板PAC-1、CD62P阳性率和血清血小板因子4水平的差异

目的 探讨脑小血管病及其亚型与大动脉粥样硬化性卒中患者血小板膜糖蛋白PAC-1和CD62P表达的差异,并对传统血小板活化标记物和炎症趋化因子血小板因子4(platelet factor 4,PF4)进行比较.方法 分别采用流式细胞术和酶联免疫吸附法测定30例大动脉粥样硬化性卒中患者、45例脑小血管病患者和30例对照者外...     

Platelet functional implications of glycoprotein Ibalpha polymorphisms in African Americans

The platelet glycoprotein Ibalpha is crucial in the binding of platelets to Von Willebrand Factor within areas of high stress. A single nucleotide polymorphism of GP Ibalpha gives rise to the Ko(a) (HPA-2b) and the -5C Kozak polymorphism. The presence of these polymorphisms has been associated with an increased risk for atherothrombotic disease. The Ko(a) polymorphism has been shown to have a higher prevalence in African Americans compared to American Caucasians. However, very little is known regarding any functional consequences of these platelet polymorphisms in African Americans. We assessed the prevalence of the Ko and -5C Kozak polymorphisms in a population of both African American and American Caucasian patients with and without CAD and determined whether there were platelet functional consequences in both groups. We studied 99 patients of which 22 were African American and 77 were American Caucasian. Aggregations were performed and shear induced platelet plug formation was tested using a platelet function analyzer. The HPA-2b allele was significantly higher in African Americans when compared to Caucasians (P = 0.001). Genotype frequencies of the -5C Kozak polymorphism were not significantly different between the two groups. We found no differences in platelet aggregation in African Americans who were either heterozygous or homozygous for the HPA-2b allele or the -5C Kozak allele when compared to American Caucasians of the same category. We found no significant differences in PFA-100 testing. We conclude from our study that these polymorphisms do not lead to altered platelet function in African Americans.     

Single nucleotide polymorphisms and inherited risk of chronic lymphocytic leukemia among African Americans

The incidence of chronic lymphocytic leukemia (CLL) is significantly lower in African Americans than whites, but overall survival is inferior. The biologic basis for these observations remains unexplored. We hypothesized that germline genetic predispositions differ between African Americans and whites with CLL and yield inferior clinical outcomes among African Americans. We examined a discovery cohort of 42 African American CLL patients ascertained at Duke University and found that the risk allele frequency of most single nucleotide polymorphisms known to confer risk of development for CLL is significantly lower among African Americans than whites. We then confirmed our results in a distinct cohort of 68 African American patients ascertained by the CLL Research Consortium. These results provide the first evidence supporting differential genetic risk for CLL between African Americans compared with whites. A fuller understanding of differential genetic risk may improve prognostication and therapeutic decision making for all CLL patients.     

Genetic variants of WNK4 in whites and African Americans with hypertension

Human chromosome 17q has been implicated to contain a gene that influences hypertension susceptibility. This region contains the WNK4 gene that causes the mendelian disorder pseudohypoaldosteronism type II, characterized by high potassium levels and hypertension. The goal of this study was to identify genetic variants in all exons of WNK4 in hypertensive individuals and to examine the association of these variants with essential hypertension. Single-nucleotide polymorphims (SNPs) were identified by sequencing the entire coding region in 32 whites and 32 African Americans with hypertension. A single SNP in whites and 8 SNPs in African Americans were genotyped in a larger cohort of whites (165 hypertensives; 91 normotensives) and African Americans (120 hypertensives; 98 normotensives). The frequency of the rare allele differed significantly between hypertensive whites (13.0%) and normotensive whites (7.1%, P=0.040) for the single intronic SNP (bp 1 156 666). This difference remained significant after adjusting for body mass index and sex (P=0.035). Genotypic frequencies differed significantly between hypertensive and normotensive individuals when a dominant model either with (P=0.027) or without (P=0.028) covariate adjustment was assumed. The odds ratio for hypertension was 2.28 for AA or AG individuals vs those with the GG genotype (95% confidence interval, 1.09 to 4.75). No significant differences in allelic or genotypic frequencies were observed in African Americans for any SNPs. The finding in whites is consistent with the hypothesis that polymorphisms in WNK4 influence the risk of hypertension. However, because the associated SNP does not appear to be a functional variant and the limitations of case/control association studies, confirmation of these results in additional cohorts is warranted.     

Variants in ABCB1, TGFB1, and XRCC1 genes and susceptibility to viral hepatitis A infection in Mexican Americans

Hepatitis A vaccination has dramatically reduced the incidence of hepatitis A virus (HAV) infection, but new infections continue to occur. To identify human genetic variants conferring a risk for HAV infection among the three major racial/ethnic populations in the United States, we assessed associations between 67 genetic variants (single nucleotide polymorphisms [SNPs]) among 31 candidate genes and serologic evidence of prior HAV infection using a population-based, cross-sectional study of 6,779 participants, including 2,619 non-Hispanic whites, 2,095 non-Hispanic blacks, and 2,065 Mexican Americans enrolled in phase 2 (1991-1994) of the Third National Health and Nutrition Examination Survey. Among the three racial/ethnic groups, the number (weighted frequency) of seropositivity for antibody to HAV was 958 (24.9%), 802 (39.2%), and 1540 (71.5%), respectively. No significant associations with any of the 67 SNPs were observed among non-Hispanic whites or non-Hispanic blacks. In contrast, among Mexican Americans, variants in two genes were found to be associated with an increased risk of HAV infection: TGFB1 rs1800469 (adjusted odds ratio [OR], 1.38; 95% confidence interval [CI], 1.14-1.68; P value adjusted for false discovery rate [FDR-P] = 0.017) and XRCC1 rs1799782 (OR, 1.57; 95% CI, 1.27-1.94; FDR-P = 0.0007). A decreased risk was found with ABCB1 rs1045642 (OR, 0.79; 95% CI, 0.71-0.89; FDR-P = 0.0007). Conclusion: Genetic variants in ABCB1, TGFB1, and XRCC1 appear to be associated with susceptibility to HAV infection among Mexican Americans. Replication studies involving larger population samples are warranted.     

Interactions of platelet factor 4 with the vessel wall

Platelet factor 4 (PF4) is a platelet-specific protein that is stored in platelet alpha granules and released following platelet activation. PF4 was the first chemokine that was isolated, but unlike other chemokines, it may not have a clear role in inflammation. Gathering evidence suggests that unlike other chemokines that bind to specific receptors, PF4's biology depends on its unusually high affinity for heparan sulfates and other negatively charged molecules at concentrations attained in the immediate vicinity of activated platelets. There has been one report that PF4 binds to CXCR3B, a chemokine receptor isoform that may be present in some vascular beds, but the biological relevance of this single observation is not clear. We propose that the main biological role of PF4 and the basis for its presence in the alpha granules of all known mammalian platelets is to neutralize surface heparan sulfate side-chains of glycosaminoglycans and to optimize thrombus development at sites of vascular injury. In addition, the binding of PF4 to surface glycosaminoglycans may also underlie its angiostatic and proatherogenic properties. Additionally, PF4 binds to several other proteins that are central to thrombosis, angiogenesis, and atherogenesis. These interactions may also contribute to its biological and pathobiological effects. Certainly, future studies using in vivo models to test biological relevance of each of these proposed mechanisms by which PF4 interacts with the vasculature are needed, as are studies to define the importance of PF4 binding to CXCR3B.     

Racial differences in initial treatment for clinically localized prostate cancer

OBJECTIVE: We examined whether there were racial differences in initial treatment for clinically localized prostate cancer and investigated whether demographic, socioeconomic, clinical, or tumor characteristics could explain any racial differences. DESIGN: Prospective cohort study. SETTING: Population-based tumor registries in Connecticut, Los Angeles, and Atlanta. PARTICIPANTS: We evaluated 1144 African-American and non-Hispanic white men, aged 50 to 74 years, with clinically localized cancer diagnosed between October 1994 and October 1995. MEASUREMENTS AND MAIN RESULTS: We obtained demographic, socioeconomic, and clinical data from patient surveys and medical record abstractions. We reported adjusted percentages for receiving treatment derived from multinomial logistic regression. We found an interaction between race and tumor aggressiveness. Among men with more aggressive cancers (PSA > or = 20 ng/mL or Gleason score > or = 8), African Americans were less likely to undergo radical prostatectomy than non-Hispanic whites (35.2% vs 52.0%), but more likely to receive conservative management (38.9% vs 16.3%, P=.003). Among the 71% of subjects with less aggressive cancers, African Americans and non-Hispanic whites were equally likely to receive either radical prostatectomy or radiation therapy (80.0% vs 84.5%, P=.2). CONCLUSIONS: African Americans with more aggressive cancers were less likely to undergo radical prostatectomy and more likely to be treated conservatively. These treatment differences may reflect African Americans' greater likelihood for presenting with pathologically advanced cancer for which surgery has limited effectiveness. Among men with less aggressive cancers-the majority of cases-there were no racial differences in undergoing radical prostatectomy or radiation therapy.     

Distinct platelet packaging, release, and surface expression of proangiogenic and antiangiogenic factors on different platelet stimuli

The present study characterized platelet secretion and surface expression of proangiogenic stromal cell-derived factor-1α (SDF-1α) and vascular endothelial growth factor (VEGF) and antiangiogenic PF4 and endostatin on activation. The angiogenic factors presented in randomly distributed granules in resting platelets, which were peripherized on activation. Confocal and immunogold electron microscopy demonstrated that SDF-1α/CXCL12 and PF4/CXCL4 mostly present in different granules. Platelet activation induced marked SDF-1α and endostatin but mild PF4 or no VEGF surface expression. PAR1-activating peptide (PAR1-AP), adenosine diphosphate (via P2Y1/P2Y12), and glycoprotein VI-targeting collagen-related peptide induced massive SDF-1α and VEGF but modest PF4 or no endostatin release. In contrast, PAR4-AP triggered marked PF4 and sole endostatin release but limited SDF-1α or VEGF secretion. Distinct platelet release of SDF-1α and endostatin involved different engagements of intracellular signaling pathways. In conclusion, different platelet stimuli evoke distinct secretion and surface expression of proangiogenic and antiangiogenic factors. PAR1, adenosine diphosphate, and glycoprotein VI stimulation favors proangiogenic, whereas PAR4 promotes antiangiogenic, factor release.     

Inverse effects of the PPAR(gamma)2 Pro12Ala polymorphism on measures of adiposity over 15 years in African Americans and whites. The CARDIA study

Few studies have addressed the association of the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor gamma 2 (PPAR gamma 2) gene with longitudinal measures of adiposity and insulin sensitivity during young adulthood, or reported on its relationship with these outcomes in African Americans. These issues were examined in the biracial Coronary Artery Risk Development in Young Adults (CARDIA) cohort, a population-based sample of 5115 African Americans and whites followed prospectively over 15 years. Frequency of the Ala12 allele was 2.1% in African Americans and 12.8% in whites, consistent with previous reports. A generalized estimating equation method was used to simultaneously examine the cross-sectional and longitudinal relationships between the Pro12Ala polymorphism and the measures of adiposity and insulin sensitivity. The Pro12Ala polymorphism was significantly associated with mean 15-year levels of adiposity, but these associations were in opposite direction in the 2 racial groups. On average, African Americans carrying the Ala12 allele had a 1.1 kg/m2 lower body mass index (BMI) ( P = .02) and whites a 0.6 kg/m2 higher BMI ( P = .01), as compared to Pro12 homozygotes. The Ala12 allele was also significantly associated with a decreased risk of incident insulin resistance syndrome in each race (OR = 0.44, P = .04 in African Americans; OR = 0.61, P = .01 in whites) and lower mean 15-year levels of fasting insulin ( P = .02), glucose ( P = .02), and homeostasis model assessment ( P = .01) in African Americans but not in whites. Important roles of BMI and ethnic background in influencing the complex relationships among PPAR gamma gene variation, adiposity, and insulin resistance are suggested.     

Preliminary report: No association between TCF7L2 rs7903146 and euglycemic-clamp-derived insulin sensitivity in a mixed-age cohort

There are conflicting reports about the significance of TCF7L2 single nucleotide polymorphism rs7903146, a single nucleotide polymorphism found to be associated with type 2 diabetes mellitus in several genomewide association studies, and insulin sensitivity. The association of rs7903146 and euglycemic-clamp-derived insulin sensitivity was tested in a cohort of children and their parents. Four hundred seventy whites (from 226 families) and 89 African Americans (from 48 families) were included in the analysis. No significant associations were seen between rs7903146 and insulin sensitivity. Adjusted genotype means were consistent across races and generational subgroups.     

Variant in the glucokinase regulatory protein (GCKR) gene is associated with fatty liver in obese children and adolescents

Recently, the single nucleotide polymorphism (SNP) identified as rs1260326, in the glucokinase regulatory protein (GCKR), was associated with hypertriglyceridemia in adults. Because accumulation of triglycerides in hepatocytes represents the hallmark of steatosis, we aimed to investigate whether this variant might be associated with fatty liver (hepatic fat content, HFF%). Moreover, because recently rs738409 in the PNPLA3 and rs2854116 in the APOC3 were associated with fatty liver, we explored how the GCKR SNP and these two variants jointly influence hepatosteatosis. We studied 455 obese children and adolescents (181 Caucasians, 139 African Americans, and 135 Hispanics). All underwent an oral glucose tolerance test and fasting lipoprotein subclasses measurement by proton nuclear magnetic resonance. A subset of 142 children underwent a fast gradient magnetic resonance imaging to measure the HFF%. The rs1260326 was associated with elevated triglycerides (Caucasians P = 0.00014; African Americans P = 0.00417), large very low-density lipoprotein (VLDL) (Caucasians P = 0.001; African Americans, P = 0.03), and with fatty liver (Caucasians P = 0.034; African Americans P = 0.00002; and Hispanics P = 0.016). The PNPLA3, but not the APOC3 rs2854116 SNP, was associated with fatty liver but not with triglyceride levels. There was a joint effect between the PNPLA3 and GCKR SNPs, explaining 32% of HFF% variance in Caucasians (P = 0.00161), 39.0% in African Americans (P = 0.00000496), and 15% in Hispanics (P = 0.00342). CONCLUSION: The rs1260326 in GCKR is associated with hepatic fat accumulation along with large VLDL and triglyceride levels. GCKR and PNPLA3 act together to convey susceptibility to fatty liver in obese youths.     

Peripheral arterial disease in African Americans: clinical characteristics, leg symptoms, and lower extremity functioning

OBJECTIVES: The describe peripheral arterial disease (PAD) in African Americans, and compare findings in African Americans and whites with PAD. DESIGN: Cross-sectional. SETTING: Three academic medical centers. PARTICIPANTS: Three hundred sixty-six whites and 76 African Americans with PAD (as defined by an ankle brachial index (ABI) <0.90) aged 55 and older identified from lower extremity arterial studies performed between 1996 and the fall of 1999. MEASUREMENTS: Comprehensive medical interview, body mass index, and neuropathy score. Functional measurements included the 6-minute walk distance, 4-m walking velocity, and the summary performance score. RESULTS: Age- and sex-adjusted results showed that African Americans had a lower mean ABI than whites (0.60 vs 0.66, P=.001), were less likely to be college graduates (13.7% vs 44.4%, P<.001), and had nearly twice the prevalence of diabetes mellitus (46.8% vs 28.0%, P=.001). After adjusting for age, sex, education level, and ABI, African Americans had a higher prevalence of no exertional leg pain (28.0% vs 18.2%, P=.044) and leg pain with exertion and rest (30.0% vs 17.3%, P=.023). African Americans had a shorter 6-minute walk distance (989 vs 1,156 ft, P<.001), a slower normal-pace 4-m walking velocity (0.79 vs 0.89 m/s, P<.001), a slower fast-pace 4-m walking velocity (1.12 vs 1.20 m/s, P=.012), and a lower summary performance score (8.8 vs 9.6, P=.018) than whites. These differences in functioning were attenuated after adjusting for age, sex, ABI, education, and leg symptoms. CONCLUSION: Poorer lower extremity functioning in African Americans was largely explained by differences in leg symptoms and, to a somewhat lesser degree, lower ABI levels and poorer education in African Americans than in whites. Further study is needed to determine whether these findings affect racial treatment disparities and poorer outcomes previously reported in African Americans than in whites with PAD.     

Relations of inflammatory biomarkers and common genetic variants with arterial stiffness and wave reflection

Inflammation causes vascular dysfunction and perpetuates proatherosclerotic processes. We hypothesized that a broad panel of inflammatory biomarkers and single nucleotide polymorphisms in inflammatory genes is associated with vascular stiffness. We assessed 12 circulating inflammatory biomarkers (C-reactive protein, fibrinogen, interleukin-6, intercellular adhesion molecule-1, lipoprotein-associated phospholipase-A2 [mass and activity], monocyte chemoattractant protein-1, myeloperoxidase, CD40 ligand, osteoprotegerin, P-selectin, and tumor necrosis factor receptor-II) in relation to tonometry variables (central pulse pressure, mean arterial pressure, forward pressure wave, reflected pressure wave, carotid-femoral pulse wave velocity, and augmentation index) measured in 2409 Framingham Heart Study participants (mean age: 60 years; 55% women; 13% ethnic/racial minorities). Single nucleotide polymorphisms (n=2195) in 240 inflammatory candidate genes were related to tonometry measures in 1036 white individuals. In multivariable analyses, biomarkers explained <1% of any tonometry measure variance. Applying backward elimination, markers related to tonometry (P<0.01) were as follows: tumor necrosis factor receptor-II (inversely) with mean arterial pressure; C-reactive protein (positively) and lipoprotein-associated phospholipase-A2 (inversely) with reflected pressure wave; and interleukin-6 and osteoprotegerin (positively) with carotid-femoral pulse wave velocity. In genetic association analyses, lowest P values (false discovery rate <0.50) were observed for rs10509561 (FAS), P=6.6x10(-5) for central pulse pressure and rs11559271 (ITGB2), P=1.1x10(-4) for mean arterial pressure. These data demonstrate that, in a community-based sample, circulating inflammatory markers tumor necrosis factor receptor-II (mean arterial pressure), C-reactive protein, lipoprotein-associated phospholipase-A2 activity (reflected pressure wave), interleukin-6, and osteoprotegerin (carotid-femoral pulse wave velocity) were significantly but modestly associated with measures of arterial stiffness and wave reflection. Additional studies are needed to determine whether variation in inflammatory marker genes is associated with tonometry measures.     

Racial similarities and differences in predictors of mobility change over eighteen months

OBJECTIVES: To define racial similarities and differences in mobility among community-dwelling older adults and to identify predictors of mobility change. DESIGN: Prospective, observational, cohort study. PARTICIPANTS: Nine hundred and five community-dwelling older adults. MEASURES: Baseline in-home assessments were conducted to assess life-space mobility, sociodemographic variables, disease status, geriatric syndromes, neuropsychological factors, and health behaviors. Disease reports were verified by review of medications, physician questionnaires, or hospital discharge summaries. Telephone interviews defined follow-up life-space mobility at 18 months of follow-up. RESULTS: African Americans had lower baseline life-space (LS-C) than whites (mean 57.0 +/- standard deviation [SD] 24.5 vs. 72.7 +/- SD 22.6; P < .001). This disparity in mobility was accompanied by significant racial differences in socioeconomic and health status. After 18 months of follow-up, African Americans were less likely to show declines in LS-C than whites. Multivariate analyses showed racial differences in the relative importance and strength of the associations between predictors and LS-C change. Age and diabetes were significant predictors of LS-C decline for both African Americans and whites. Transportation difficulty, kidney disease, dementia, and Parkinson's disease were significant for African Americans, while low education, arthritis/gout, stroke, neuropathy, depression, and poor appetite were significant for whites. CONCLUSIONS: There are significant disparities in baseline mobility between older African Americans and whites, but declines were more likely in whites. Improving transportation access and diabetes care may be important targets for enhancing mobility and reducing racial disparities in mobility.     

Single‐nucleotide polymorphisms in tumor necrosis factor receptor genes: Definition of novel haplotypes and racial/ethnic differences

Objective

To characterize allele frequencies of known single‐nucleotide polymorphisms (SNPs) in tumor necrosis factor receptor (TNFR) genes in African Americans with rheumatoid arthritis (RA), healthy African Americans, and healthy Caucasians.

Methods

One TNFRSF1B SNP (196 G/T) that influences susceptibility to familial RA in Caucasians and 3 SNPs in the 5′ flanking region of the TNFRSF1A gene (‐609G/T, ‐580A/G, and ‐383A/C) were genotyped in 108 African Americans with RA, 62 healthy African Americans, and 59 healthy Caucasians.

Results

There were no differences in TNFRSF1A allele frequencies between African Americans with RA and healthy African Americans. Allele frequencies were strikingly different, however, between healthy African Americans and healthy Caucasians: 0.13 versus 0.42 for ‐609T, 0.49 versus 0 for ‐580G, and 0.14 versus 0 for ‐383C. We identified 4 novel haplotypes defined by the 3 TNFRSF1A SNPs, the distribution of which was markedly different in healthy Caucasians and healthy African Americans (P = 0.000001 by chi‐square test‐. The frequencies of the TNFRSF1B 196 genotypes were similar in African Americans with RA and healthy African Americans but differed between healthy African Americans and healthy Caucasians (P = 0.05).

Conclusion

Although we observed no associations between known TNFR SNPs or haplotypes and RA, significant racial differences were observed at both loci. Comparison of these data with other published frequencies of TNFRSF1A and TNFRSF1B genotypes according to race suggests that the distribution in African American, Caucasian, and Asian populations differs significantly. These striking racial/ethnic differences in TNFR SNP frequencies may influence the likelihood of familial RA, severe disease, or response to TNF inhibitors and may have important evolutionary implications.

     

The prothrombotic potential of platelet factor 4

Heparin-induced thrombocytopenia (HIT) is a prothrombotic disorder initiated by heparin administration. It is caused by the formation of pathogenic antibodies to complexes of platelet factor-4 (PF4) and heparin on platelet surfaces that cause platelet activation, aggregation and thrombosis. There has been intense research on this intriguing, drug-related thrombocytopenia explaining several characteristic aspects of this condition. However, prothrombotic potential of the key player, PF4 has not been investigated in many studies although it has been shown to be critical in monocyte chemotaxis, monocyte–platelet interaction, and megakaryocyte suppression, all of which can contribute to the pathophysiology of HIT. This article explains the important role of PF4 released during platelet activation with the administration of heparin in the pathogenesis of thrombocytopenia and thrombosis in HIT.     

Epidemiology of irritable bowel syndrome among African Americans as compared with whites: a population-based study.

BACKGROUND & AIMS: We studied the prevalence as well as the sociodemographic characteristics and quality of life of African American patients with irritable bowel syndrome (IBS) among the population at large and compared them with those of whites. METHODS: A total of 990 adults from 9 different sites in the Jackson, Mississippi metropolitan area (670 African Americans and 320 whites) completed self-administered questionnaires providing sociodemographic information and details regarding bowel habits and associated symptoms for diagnosing IBS on the basis of Rome II criteria. Quality of life was assessed by the SF-12 questionnaire. RESULTS: Ninety-five of the 990 participants had IBS, giving a total sample prevalence of 9.6% (African Americans, 7.9%; whites, 13.1%). Adjusting for other risk factors in a reduced logistic regression model, we found race (P = .0004) and education (P = .0049) to be important correlates of IBS prevalence. The household income showed a trend toward statistical significance (P = .0845). With the adjusted odds ratio as an estimate of relative risk, whites were 2.5 (95% confidence interval, 1.5-4.0) more likely than African Americans to have IBS. In terms of an index for quality of life (possible score, 1-44), the adjusted mean score was lower for adults with IBS compared with non-IBS adults (IBS mean, 29.8; no IBS, 34.2; P < .0001), but the racial difference was not significant. CONCLUSIONS: IBS occurs less frequently among African Americans. Although IBS affects quality of life among both ethnicities, the degree of impairment is similar.