Racial Differences In Susceptibility Research Articles

Primary hyperparathyroidism: insights from the Indian PHPT registry.

The presentation of primary hyperparathyroidism (PHPT) is variable throughout the world. The present study explored retrospective data submitted to the Indian PHPT registry ( http://www.indianphptregistry.com ) between July 2005 and June 2015 from 5 centres covering four different geographical regions. The clinical, biochemical, radiological and histopathological characteristics of PHPT patients across India were analysed for similarity and variability across the centres. A total of 464 subjects (137 men and 327 women) with histopathologically proven PHPT were analysed. The mean age was 41±14years with a female:male ratio of 2.4:1. The majority (95%) of patients were symptomatic. Common clinical manifestations among all the centres were weakness and fatigability (58.7%), bone pain (56%), renal stone disease (31%), pancreatitis (12.3%) and gallstone disease (11%). Mean serum calcium, parathyroid hormone and inorganic phosphorus levels were 11.9±1.6mg/dL, 752.4±735.2pg/mL and 2.8±0.9mg/dL, respectively. Sestamibi scanning had better sensitivity than ultrasonography in the localisation of parathyroid adenoma; however, when these two modalities were combined, 93% of the cases were correctly localised. Mean parathyroid adenoma weight was 5.6±6.5g (0.1-54g). It was concluded that the majority of PHPT patients within India are still mainly symptomatic with >50% of patients presenting with bone disease and one-third with renal impairment. Compared to Western countries, Indian patients with PHPT are younger, biochemical abnormalities are more severe, and adenoma weight is higher. As our observation is largely derived from a tertiary care hospital (no routine screening of serum calcium level), the results do not reflect racial differences in susceptibility to PHPT.

Racial Differences in the Clinical Profile, Causes, and Outcome of Chronic Pancreatitis.

Racial differences in susceptibility and progression of pancreatitis have been reported in epidemiologic studies using administrative or retrospective data. There has been little study, however, on the clinical profile, causes, and outcome of chronic pancreatitis (CP) in black patients. We analyzed data on black patients with CP prospectively enrolled in the multicenter North American Pancreatitis Studies from 26 US centers during the years 2000-2014. CP was defined by definitive evidence on imaging studies or histology. Information on demographics, etiology, risk factors, disease phenotype, treatment, and perceived effectiveness was obtained from responses to detailed questionnaires completed by both patients and physicians. Of the 1,159 patients enrolled, 248 (21%) were black. When compared with whites, blacks were significantly more likely to be male (60.9 vs. 53%), ever (88.2 vs. 71.8%), or current smokers (64.2 vs. 45.9%), or have a physician-defined alcohol etiology (77 vs. 41.9%). There was no overall difference in the duration of CP although for alcoholic CP, blacks had a longer duration of disease (8.6 vs. 6.97 years; P=0.02). Blacks were also significantly more likely to have advanced changes on pancreatic morphology (calcifications (63.3 vs. 55.2%), atrophy (43.2 vs. 34.6%), pancreatic ductal stricture or dilatation (72.6 vs. 65.5%) or common bile duct stricture (18.6 vs. 8.2%)) and function (endocrine insufficiency 39.9 vs. 30.2%). Moreover, the prevalence of any (94.7 vs. 83%), constant (62.6 vs. 51%), and severe (78.4 vs. 65.8%) pain and disability (35.1 vs. 21.4%) were significantly higher in blacks. Observed differences were in part related to variances in etiology and duration of disease. No differences in medical or endoscopic treatments were seen between races although prior cholecystectomy (31.1 vs. 19%) was more common in white patients. Differences were observed between blacks and whites in the underlying cause, morphologic expression, and pain characteristics of CP, which in part are explained by the underlying risk factor(s) with alcohol and tobacco being much more frequent in black patients as well as disease duration.

Poor Sleep Quality and Associated Inflammation Predict Preterm Birth: Heightened Risk among African Americans

Poor sleep promotes inflammation. In turn, inflammation is a causal mechanism in term as well as preterm parturition. In the United States, a persistent racial disparity in preterm birth exists, with African Americans showing ∼1.5 times greater risk. This study examined associations among sleep quality, serum proinflammatory cytokines, and length of gestation in a racially diverse sample of 138 pregnant women. Observational. Women completed the Pittsburgh Sleep Quality Index (PSQI) and other psychosocial and behavioral measures during midpregnancy. Serum levels of interleukin (IL)-6, IL-8, IL-1β, and tumor necrosis factor (TNF)-α were determined by high-sensitivity assays. Birth outcomes were determined via medical record review. Among African American women (n = 79), shorter gestation was predicted by poorer overall sleep (rs = -0.35, P = 0.002) as well the following PSQI subscales: subjective sleep quality (rs = -0.34, P = 0.002), sleep latency (rs = -0.27, P = 0.02), and sleep efficiency (rs = -0.27, P = 0.02). African American women with poor sleep quality (PSQI > 5) had 10.2 times the odds of preterm birth compared to those with good sleep quality. In contrast, among European American women (n = 53), gestational length was not significantly predicted by sleep quality (Ps > 0.12). Bootstrapping analyses showed that, among African Americans, IL-8 significantly mediated the association between sleep quality and length of gestation (indirect effect estimate -0.029; 95% confidence interval -0.06, -0.002). The data provide novel evidence that African American women exhibit greater inflammation in response to sleep disturbance than European American women and these effects correspond with length of gestation. Racial differences in susceptibility to sleep induced immune dysregulation may contribute to marked racial disparities in preterm birth.

More than skin deep: connecting melanocyte pigmentation and angiogenic diseases

Epidemiological studies have identified racial differences in susceptibility to numerous diseases, including several ocular and skin diseases characterized by increased vascular growth. In most cases, the specific mechanisms and genetic variants responsible for these differences have remained elusive. In this issue of the JCI, Adini et al. explore a direct connection between skin pigmentation and susceptibility to angiogenic diseases and identify an extracellular matrix protein that is regulated by melanogenesis and potently modulates angiogenesis.

Admixture Mapping of Coronary Artery Calcified Plaque in African Americans With Type 2 Diabetes Mellitus

The presence and severity of coronary artery calcified plaque (CAC) differs markedly between individuals of African and European descent, suggesting that admixture mapping may be informative for identifying genetic variants associated with subclinical cardiovascular disease. Admixture mapping of CAC was performed in 1040 unrelated African Americans with type 2 diabetes mellitus from the African American-Diabetes Heart Study, Multi-Ethnic Study of Atherosclerosis and Family Heart Study using the Illumina custom ancestry informative marker panel. All cohorts obtained computed tomography scanning of the coronary arteries using identical protocols. For each ancestry informative marker, the probability of inheriting 0, 1, and 2 copies of a European-derived allele was determined. Linkage analysis was performed by testing for association between each ancestry informative marker using these probabilities and CAC, accounting for global ancestry, age, sex, and study. Markers on 1p32.3 in the GLIS1 gene (rs6663966, logarithm of odds [LOD]=3.7), 1q32.1 near CHIT1 (rs7530895, LOD=3.1), 4q21.2 near PRKG2 (rs1212373, LOD=3.0), and 11q25 in the OPCML gene (rs6590705, LOD=3.4) had statistically significant LOD scores, whereas markers on 8q22.2 (rs6994682, LOD=2.7), 9p21.2 (rs439314, LOD=2.7), and 13p32.1 (rs7492028, LOD=2.8) manifested suggestive evidence of linkage. These regions were uniformly characterized by higher levels of European ancestry associating with higher levels or odds of CAC. Findings were replicated in 1350 African Americans without diabetes mellitus and 2497 diabetic European Americans from Multi-Ethnic Study of Atherosclerosis and the Diabetes Heart Study. Fine mapping these regions will likely identify novel genetic variants that contribute to CAC and clarify racial differences in susceptibility to subclinical cardiovascular disease.

Atrial Electrical and Structural Remodeling: Implications for Racial Differences in Atrial Fibrillation

Racial Disparity in AF Electrophysiology. Racial differences in prevalence and incidence rates of atrial fibrillation (AF) are known to exist even after accounting for ascertainment bias, as well as differences in the prevalence of known risk factors. Thus, a different susceptibility to traditional risk factors in different ethnic groups that lead to AF clearly exists. Initiation and maintenance of AF are dependent on triggers, autonomic influence and atrial substrate, and progression to persistent AF occurs by electromechanical remodeling. Genetic differences among the racial group contribute to such differences. This article reviews the electrophysiologic mechanisms for AF, evidence for racial differences in susceptibility to AF, and suggests possible electromechanical reasons for the susceptibility.

Racial differences in susceptibility to infection by Mycobacterium tuberculosis

A person’s state of health is a key resource for living a fulfilling and rewarding life. The term ‘health’ encompasses a person’s physical, mental, and social capabilities. Regardless of age, a person’s health depends on his or her ability to maintain homeostasis, adapt to adverse situations, and maintain relationships. However, many Americans define their own […]

ワルファリン治療個別化に利用可能な簡易・同時遺伝子診断法の確立

Identification of the gene encoding human vitamin K epoxide reductase complex subunit 1 (VKORC1 ),the main target molecule of coumarin derivatives,has contributed to clarifying racial differences in susceptibility to warfarin (Wf).However,although the discovery of genetic polymorphisms of the VKORC1 gene greatly aided understanding of the causes of great inter-individual variation in the response to Wf,a means of determining the optimal maintenance dose of the drug for each patient has not yet been established.From the viewpoint of application to both research and routine laboratory testing in the near future,we established a rapid and simple,simultaneous genotyping method for 2 known critical genetic factors,VKORC1 and CYP2C9 .The basic principle of this method is multi-primer PCR in which the genotypes of these genes are determined within 2 hr using a single thermal cycling condition.The intensity of the band amplified from the CYP2C9*3 allele is much greater than that obtained with the method currently used,indicating that the new method would be advantageous in visual diagnosis.Furthermore,since this method was applicable to non-blood derived samples,it would be suitable for a wide variety of patients whose blood is hard to collect,such as small children suffering from Kawasaki disease,or those with few leucocytes due to the adverse effects of chemotherapy with anti-cancer agents.

Population Differences in Elastin Maturation in Optic Nerve Head Tissue and Astrocytes

Glaucomatous optic neuropathy is characterized by remodeling of the extracellular matrix with disorganization of elastic fibers in the optic nerve head (ONH). There are significant differences in prevalence of glaucomatous optic neuropathy between African Americans (AAs) and Caucasian Americans (CAs). The goal of this study was to evaluate differences in elastin synthesis and maturation in ONH tissue and cells of AA and CA donors with no eye disease, to provide a basis for underlying racial differences in susceptibility to elevated intraocular pressure. The amount of mature elastin in ONHs from each group of donors was evaluated by desmosine radioimmunoassay. The distribution of elastic fibers in ONH tissue was investigated by immunofluorescent staining. Elastin and lysyl oxidase mRNA levels and alternative splicing of elastin in ONH astrocytes were investigated by quantitative PCR. Tropoelastin protein expression was assessed by immunoblot analysis. ONHs from AA donors had significantly reduced levels of desmosine compared with those of CAs. In contrast, elastin mRNA and tropoelastin synthesis were elevated in ONH astrocytes from AA individuals. The inclusion of exon 23 in elastin mRNA and lysyl oxidase-like 2 mRNA levels was significantly reduced in astrocytes from AA compared with CA donors. A reduced number of cross-linking domains in elastin and decreased lysyl oxidase-like 2 expression leads to decreased amount of mature elastin in ONHs from healthy AA individuals compared with CA donors. These results suggest ELN and LOXL2 as candidate susceptibility genes for population-specific genetic risk of primary open-angle glaucoma (POAG).

Racial differences in susceptibility to obesity

Racial differences in susceptibility to obesity

Role of HLA class II alleles in Korean patients with IDDM

MHC associations with IDDM in the Korean population were studied to investigate genetic susceptibility to this disorder. The frequencies of HLA-DR3, -DR4 and -DR9 were significantly higher in diabetic patients. However, the frequency of DR2 was significantly decreased in diabetic patients. DQA1 ∗0301 and DQA1 ∗0501 were positively and DQA1 ∗0102 and DQA1 ∗0201 negatively associated with IDDM. DQB1 ∗0301 and DQB1 ∗0601 were negatively associated with IDDM. Heterodimers DQA1 ∗0301-DQB1 ∗0201, DQA1 ∗0501-DQB1 ∗0201 and DQA1 ∗0501-DQB1 ∗0302 were positively associated and DQA1 ∗0102-DQB1 ∗0601 negatively associated with IDDM. The frequencies of DR3-DQA1 ∗0301-DQB1 ∗0201 and -DQA1 ∗0501-DQB1 ∗0201 were significantly higher in diabetic patients. The frequencies of DR4-DQA1 ∗0301-DQB1 ∗0201 and DR9-DQA1 ∗0301-DQB1 ∗0303 were significantly higher in diabetic patients. The presence of non-aspartic acid at position 57 of the DQβ-chain was not associated with susceptibility to IDDM. However, the frequency of Arg 52 homozygotes was significantly higher in diabetic patients. These results suggest a role of the MHC molecule and also suggest racial differences in susceptibility to IDDM even within the Asian populations.

Institutional Control Measures for Tuberculosis in the Era of Multiple Drug Resistance: ACCP/ATS Consensus Conference

Institutional Control Measures for Tuberculosis in the Era of Multiple Drug Resistance: ACCP/ATS Consensus Conference

Racial and Age-related Differences in Incidence and Severity of Focal Autoimmune Thyroiditis

To determine possible racial and age-related differences of focal autoimmune thyroiditis between white and black Americans, autopsy material from American subjects was evaluated for incidence and severity of chronic lymphocytic thyroiditis. The overall incidence of lymphocytic infiltration in thyroid sections from subjects aged more than 20 years was 41.4% in white females, 20% in white males, 17.4% in black females, and 8.5% in black males. An increase to 54.8% in incidence of thyroiditis from the first decade onward was noted in white females older than 80 years of age. Age did not cause a remarkable increase in incidence of thyroiditis in white males, in black females, or black males. The susceptibility to chronic thyroiditis in American white males and females was almost the same as that of British white males and females. The incidence of thyroiditis in black females and males was similar to that in Japanese females and males. These findings showed clear racial differences in susceptibility to chronic thyroiditis.

Is focal chronic autoimmune thyroiditis an age‐related disease? Differences in incidence and severity between Japanese and British

The incidence of chronic lymphocytic thyroiditis in autopsy material from Japanese and British subjects was evaluated. Lymphocytic infiltration in representative thyroid sections from 1826 Japanese cases collected from four different institutions was analysed. The overall incidence of lymphocytic infiltration was significantly higher in females (22.2 per cent) than in males (13.9 per cent). In females, the incidence reached 23.2 per cent in the fourth decade and showed no increase with age thereafter. The overall incidence of lymphocytic infiltration in thyroid sections from 810 British cases was 42.5 per cent in females and 19.4 per cent in males; an increase in the incidence of thyroiditis from the sixth decade onwards was noted in British females, the figure reaching 50.0 per cent in those aged over 70 years. These findings suggest possible racial differences in susceptibility to chronic thyroiditis. The disorder is not necessarily related to age, increasing severity of disease with age being found only in British females.

Racial differences in susceptibility to infection by Mycobacterium tuberculosis: Stead WW, Senner JW, Reddick WT, et al: N Engl J Med 322:422–427, 1990

Racial differences in susceptibility to infection by Mycobacterium tuberculosis: Stead WW, Senner JW, Reddick WT, et al: N Engl J Med 322:422–427, 1990

Racial Differences in Susceptibility to Infection byMycobacterium tuberculosis

The prevalence of tuberculosis among blacks is known to be about twice that among whites. When we looked at infection rates among the initially tuberculin-negative residents of 165 racially integrated nursing homes in Arkansas, we were stimulated to investigate whether this difference could be due in part to racial differences in susceptibility to Mycobacterium tuberculosis infection. A new infection was defined by an increase of greater than or equal to 12 mm of induration after a tuberculin skin test (5 tuberculin units) administered at least 60 days after a negative two-step test. On repeat skin testing of the 25,398 initially tuberculin-negative nursing home residents, we found that 13.8 percent of the blacks and only 7.2 percent of the whites had evidence of a new infection (relative risk, 1.9; 95 percent confidence interval, 1.7 to 2.1). Blacks were infected more frequently, regardless of the race of the source patient. In homes with a single source patient who was white, 17.4 percent of the black and 11.7 percent of the white residents became infected (relative risk, 1.5; 95 percent confidence interval, 1.2 to 1.9); in homes with a single source patient who was black, 12.4 percent of the black and 7.7 percent of the white residents became infected (relative risk, 1.6; 95 percent confidence interval, 1.2 to 2.1). However, there was no racial difference in the percentage of residents who had recently converted to positive status who, in the absence of preventive therapy, were later found to have clinical tuberculosis (blacks, 11.5 percent; whites, 10.6 percent). Data from three outbreaks of tuberculosis in two prisons also showed that blacks have about twice the relative risk of whites of becoming infected with M. tuberculosis. We conclude that blacks are more readily infected by M. tuberculosis than are whites. The data also suggest that susceptibility to M. tuberculosis infection varies independently of the factors governing the progression to clinical disease.

Racial differences in susceptibility to tuberculosis: Risk of disease after infection

It is generally believed that certain racial groups are highly susceptible to tuberculosis disease while others have developed a “natural resistance.” Epidemiological studies reporting differences in case rates among different racial groups, provide inconclusive evidence. Many factors influence the development of active tuberculosis including sex, age, body weight, and virulence of the infecting organism. These, as well as other factors, may be more important determinants which, up to now, have been confused with race.

The Enigma of Coronary Heart Disease

Deaths are rarely certified, as they were in 1900, as due to myocardial degeneration or senility. It is far more fashionable to cite arteriosclerotic heart disease, even when mode of death is uncertain. A death certificate is demanded, duly signed, and states the cause of death, irrespective of whether this can be more than conjecture. Autopsy rooms do bear witness to increasing prevalence of coronary disease, but population of autopsy rooms has changed —survival to age 45 has increased nearly threefold since 1900. Furthermore, comparison with past observations is fraught with technical and statistical booby traps. These considerations and many others have led Dr. Robb-Smith to an incisive critique of contemporary belief in a modern epidemic of coronary heart disease. While granting validity of evidence for great racial differences in susceptibility (probably a more productive field for investigation), he attributes our increased prevalence of ischemic heart disease

RACIAL AND SOCIAL FACTORS IN SYSTEMIC LUPUS ERYTHEMATOSUS.

An epidemiologic study of systemic lupus erythematosus in a defined area of New York revealed significant racial differences in susceptibility. Morbidity and mortality rates were highest among Negroes residing in the area studied, followed in descending order by the rates for Puerto Ricans and then other whites. Confirmatory data were obtained on a city-wide basis from reported deaths and on a national level from discharged patients of Veterans Administration hospitals. The racial differences observed in New York were independent of poor housing, overcrowding, and migration. They were associated with racial differences in γ-globulin levels of normal individuals.

Racial differences in susceptibility to tuberculosis

Racial differences in susceptibility to tuberculosis