Characterization of greater middle eastern genetic variation for enhanced disease gene discovery

The Greater Middle East (GME) has been a central hub of human migration and population admixture. The tradition of consanguinity, variably practiced in the Persian Gulf region, North Africa, and Central Asia1-3, has resulted in an elevated burden of recessive disease4. Here we generated a whole-exome GME variome from 1,111 unrelated subjects. We detected substantial diversity and admixture in continental and subregional populations, corresponding to several ancient founder populations with little evidence of bottlenecks. Measured consanguinity rates were an order of magnitude above those in other sampled populations, and the GME population exhibited an increased burden of runs of homozygosity (ROHs) but showed no evidence for reduced burden of deleterious variation due to classically theorized ‘genetic purging’. Applying this database to unsolved recessive conditions in the GME population reduced the number of potential disease-causing variants by four- to sevenfold. These results show variegated genetic architecture in GME populations and support future human genetic discoveries in Mendelian and population genetics

Effect of body mass index on quality of life in allergic/asthmatic patients

24th Congress of the European-Academy-of-Allergology-and-Clinical-Immunology -- JUN 26-JUL 01, 2005 -- Munich, GERMANYWOS: 000242195700012PubMed: 17176785Evaluation of quality of life (QoL) is of particular interest in patients suffering from chronic diseases. Although studies have shown an association between QoL and obesity and allergy/asthma, the effect of obesity on QoL is not well known. The aim of this study was to assess the impact of body mass index (BMI) as a contributory factor on QoL in patients with a diagnostic label of allergy/asthma. We surveyed 100 patients (69 F/31 M) (age 34.15 +/- 13.32 years), and 65 healthy controls (42 F/23 M) (age 35.45 +/- 8.96 years). QoL was determined by SF-36. BMI >= 25 kg/m(2) was accepted as overweight/obesity. Forty-five percent of the patients had BMI >= 25 kg/m(2) with no difference between the genders. They were significantly older and more likely to have less education level than those with BMI < 25 kg/m(2). Quality-of-life scores among patients with allergy/asthma were lower than those in the control group, irrespective of BMI. However, increased BMI was found to be related with improved quality of life among controls. Pearson's analysis showed that BMI was inversely correlated with physical functioning among patients (r = -0.229, p = 0.034), but in the control group it was positively correlated with QoL. All the domains of SF-36, except role-physical ones, among female subjects were significantly impaired more than those of male patients. It has been shown that the major determinants of impaired QoL are female sex, older age, and less educational status in patients with allergic/asthmatic symptoms. The impact of BMI on QoL could be undermined, because it seems to play a minor role.European Acad Allergol Clin Immuno

Perception of dyspnea during exacerbation and histamine-related bronchoconstriction in patients with asthma

WOS: 000237857400014PubMed: 16729784Background: Numerous studies have been performed concerning the perception of dyspnea during changes in airway caliber provoked in the laboratory setting, but studies of asthma exacerbation are scarce. Objective: To investigate whether the perception of dyspnea during histamine-induced bronchoconstriction might be used to identify patients with asthma who sense dyspnea poorly during exacerbation. Methods: The perception of dyspnea in 50 patients (45 female, 5 male) with asthma was evaluated at admission with exacerbation and during a stable period. Perceived intensity of dyspnea was estimated using a modified Borg scale. The perception of dyspnea in the stable period 4 to 6 weeks after exacerbation was measured with the histamine challenge test. Perception parameters were defined as the change in Borg score divided by the change in forced expiratory volume in 1 second (FEV1) as a percentage of the baseline FEV1 (Delta Borg/Delta FEV1) and as the Borg score at 20% decrease (PS20Histamine) or increase (PS20Exacerbation) in FEV1. Results: The perception of dyspnea during asthma exacerbation was unrelated to the perception of dyspnea during histamine-induced bronchoconstriction (for Delta Borg/Delta FEV1, beta = .08, P = .50; for PS20, beta = -.11, P = .40). The K value for the agreement of poor perceivers at exacerbation and during the stable period was -0.21 (P = .10). However, the intensity of dyspnea caused by histamine-induced bronchoconstriction was lower than that caused by asthma exacerbation (PS20: 1.6 +/- 1.1 vs 2.8 +/- 2.5. respectively. P = .004; Delta Borg/Delta FEV1: 0.08 +/- 0.05 vs 0.21 +/- 0.28, respectively, P = .001). Conclusion: The perception of dyspnea during asthma exacerbation is not correlated with the perception of dyspnea during histamine-induced bronchoconstriction. Therefore, the perception of dyspnea during histamine-induced bronchoconstriction cannot be used to identify the asthmatic patients who perceive dyspnea poorly