TNFSF4 polymorphisms are associated with systemic lupus erythematosus in the Malaysian population

Tumour necrosis factor superfamily 4 (TNFSF4) gene has been reported to be associated with systemic lupus erythematosus (SLE) susceptibility due to its encoding for OX40L protein that can increase autoantibody production and cause imbalance of T‐cell proliferation. The purpose of this study was to investigate the association of TNFSF4 rs2205960, rs1234315, rs8446748 and rs704840 with SLE in the Malaysian population. A total of 476 patients with SLE and 509 healthy controls were recruited. Real‐time polymerase chain reaction (PCR) was applied to genotype the selected single nucleotide polymorphisms (SNPs). Allelic and genotypic frequencies of each SNP were calculated for each ethnic group, and association test was performed using logistic regression. The overall association of each SNP in Malaysian patients with SLE was determined with meta‐analysis. The frequency of minor T allele of TNFSF4 rs2205960 was significant in Chinese and Indian patients with SLE, with P values of 0.05 (OR = 1.27, 95% CI: 1.00–1.61) and 0.004 (OR = 3.16, 95% CI: 1.41–7.05), respectively. Significant association of minor G allele of rs704840 with SLE was also observed in Chinese (P = 0.03, OR = 1.26, 95% CI: 1.02–1.56). However, after Bonferroni correction, only T allele of rs2205960 remained significantly associated with Indian cohort. Overall, minor G allele of rs704840 showed significant association with SLE in the Malaysian population with P values of 0.05 (OR = 1.20, 95% CI: 1.00–1.43). We suggested TNFSF4 rs704840 could be the potential SLE risk factors in the Malaysian population.     

Familial aggregation of food allergy and sensitization to food allergens: a family-based study

Background The increasing prevalence of food allergy (FA) is a growing clinical and public health problem. The contribution of genetic factors to FA remains largely unknown. Objective This study examined the pattern of familial aggregation and the degree to which genetic factors contribute to FA and sensitization to food allergens. Methods This study included 581 nuclear families (2,004 subjects) as part of an ongoing FA study in Chicago, IL, USA. FA was defined by a set of criteria including timing, clinical symptoms obtained via standardized questionnaire interview and corroborative specific IgE cut‐offs for 95% positive predictive value (PPV) for food allergens measured by Phadia ImmunoCAP. Familial aggregation of FA as well as sensitization to food allergens was examined using generalized estimating equation (GEE) models, with adjustment for important covariates including age, gender, ethnicity and birth order. Heritability was estimated for food‐specific IgE measurements. Results FA in the index child was a significant and independent predictor of FA in other siblings (OR=2.6, 95% CI: 1.2–5.6, P=0.01). There were significant and positive associations among family members (father–offspring, mother–offspring, index–other siblings) for total IgE and specific IgE to all the nine major food allergens tested in this sample (sesame, peanut, wheat, milk, egg white, soy, walnut, shrimp and cod fish). The estimated heritability of food‐specific IgE ranged from 0.15 to 0.35 and was statistically significant for all the nine tested food allergens. Conclusion This family‐based study demonstrates strong familial aggregation of FA and sensitization to food allergens, especially, among siblings. The heritability estimates indicate that food‐specific IgE is likely influenced by both genetic and environmental factors. Together, this study provides strong evidence that both host genetic susceptibility and environmental factors determine the complex trait of IgE‐mediated FA.     

Exposure to ‘farming’ and objective markers of atopy: a systematic review and meta‐analysis

There is growing interest in the ‘farm effect’ on the spectrum of allergy. Evidence concerning the farm effect on asthma, eczema, and allergic rhinitis has been systematically synthesized, but without a specific focus on objective markers of sensitization. This focus is important, as farm exposures may be related to allergy but not to non‐allergic phenotypes of disease. We aimed to systematically review and meta‐analyse literature that has investigated associations between farm exposure at any age and objective measures of atopy, that is serum IgE or skin prick tests results. Using predefined inclusion and exclusion criteria, we identified 29 articles for review. IgE levels were measured in either childhood or adulthood by eighteen studies, while skin prick testing was performed in sixteen studies. Newcastle‐Ottawa Scale quality assessments indicated that the majority of these studies demonstrated a representative sample of selected participants. Due to significant heterogeneity in study measures and methodology between studies, only few were meta‐analysed. This meta‐analysis showed a significant protective effect of farm exposure before 1 year of life on allergic sensitization (OR = 0.60 [0.52–0.70]). Farm exposure during childhood was also associated with a reduced risk of sensitization to cat or timothy (OR = 0.60 [0.51–0.70]; OR=0.46 [0.41–0.51]). Studies investigating the effect of farm exposure in adult life could not be meta‐analysed, and their results were inconsistent. Insufficient studies investigated food sensitization as an outcome to allow synthesis. The majority of studies included in this review investigated childhood farm exposure, finding evidence to support a protective childhood ‘farm effect’ against subsequent atopy. There is inconsistent evidence on the association between farm exposure in adulthood and allergic sensitization. Further studies are needed to tease out the exact exposures and timing associated with farming environments that protect against allergic disease.     

Perinatal risk factors for sensitization, atopic dermatitis and wheezing during the first year of life (PIPO study)

Objective To evaluate the influence of perinatal environmental factors on early sensitization, atopic dermatitis and wheezing during the first year. Methods Information on pregnancy‐related factors, parental atopic history, environmental factors and the clinical course of the infant until age one was gathered by questionnaires, as part of a prospective birth cohort study (Prospective study on the Influence of Perinatal factors on the Occurrence of asthma and allergies [PIPO‐study]). Quantification of total and specific IgE was performed in 810 children and their parents. Results Early sensitization was found in 107/810 (13%) of the infants. Multiple regression analysis showed that specific IgE in fathers was a risk factor for early sensitization in their daughters (adjusted odds ratios (OR_adj) 2.21 (95% confidence interval (CI) 1.10–4.49); P=0.03), whereas in boys, day care attendance was shown to be protective for early sensitization (OR_adj 0.38 (95% CI 0.20–0.71); P=0.001). Atopic dermatitis occurred in 195/792 infants (25%). Specific IgE in the mother (OR_adj 1.52 (95% CI 1.06–2.19); P=0.02) and in the infant (OR_adj 4.20 (95% CI 2.63–6.68); P<0.001) were both risk factors for the occurence of atopic dermatitis, whereas postnatal exposure to cats was negatively associated with atopic dermatitis (OR_adj 0.68 (0.47–0.97); P=0.03). Postnatal exposure to cigarette smoke (OR_adj 3.31 (95% CI 1.79–6.09); P<0.001) and day care attendance (OR_adj 1.96 (95% CI 1.18–3.23); P=0.009) were significantly associated with early wheezing, which occurred in 25% (197/795) of the infants. Conclusion The effect of paternal sensitization and day care attendance on sensitization is gender dependent. Maternal sensitization predisposes for atopic dermatitis, whereas postnatal exposure to cats had a protective effect.     

IL33 and IL1RL1 variants are associated with asthma and atopy in a Brazilian population

Atopic asthma is a chronic inflammatory disease in airways resulting from genetic and environmental factors, characterized by production of the Th2 cytokines interleukin‐4 (IL‐4), interleukin‐5 (IL‐5) and interleukin‐13 (IL‐13). Interleukin‐33 (IL‐33) appears to be a potent inducer of Th2 immune response. This occurs when IL‐33 binds and activates its receptor, the membrane ST2 (ST2L) in mast cells, dendritic cells, basophils, eosinophils, innate lymphoids and Th2 cells, leading to the release of these cytokines and intensifying allergic inflammation. Polymorphisms in the IL33 and IL1RL1 can act as protective or risk factors for asthma and/or allergy in humans. No study was conducted to replicate such findings in a European and African descendent mixed population. DNA was extracted from peripheral blood from 1223 subjects, and the samples were genotyped using Illumina 2.5 Human Omni Beadchip. We tested for possible associations between SNPs in the IL33 and ST2 with asthma and allergy markers such as specific IgE (sIgE), IL‐5 and IL‐13 production and skin prick test (SPT). Logistics regressions were performed using PLINK software 1.07. The analyses were adjusted for sex, age, helminth infection and ancestry markers. The G allele of IL33 SNP rs12551256 was negatively associated with asthma (OR 0.71, 95% CI: 0.53–0.94, P = 0.017). In contrast, the A allele of IL1RL1 rs1041973 was positively associated with IL‐5 production (OR 1.36, 95% CI: 1.09–1.84, P = 0.044), sIgE levels (OR 1.40, 95% CI: 1.07–1.84, P = 0.013) and positive SPT (OR 1.48, 95% CI: 1.08–2.03, P = 0.014), for Blomia tropicalis mite. The same allele, in atopic subjects, was associated with decreased production of soluble ST2 (sST2) (P < 0.05). Moreover, expression quantitative trait loci (eQTL) analysis suggests that rs1041973 and rs873022 regulate the expression of IL1RL1 gene. This latest SNP, rs873022, the T allele, was also associated with a lower production of sST2 in plasma of Brazilians. The genetic risk score for rs1041973 and rs16924161 demonstrated a higher risk for SPT positivity against B. tropicalis, the greater the number of risk alleles for both SNPs. Our findings demonstrate a robust association of genetic variants in IL1RL1 and IL33 SNPs with allergy markers and asthma.     

Association of single nucleotide polymorphisms in TPM1 rs11071720, rs3803499, rs12148828, and rs1972041 with the risk of nonsyndromic cleft lip with or without cleft palate in a sample of the Iranian population,a preliminary report

Several lines of evidence support an association between tropomyosin 1 (TPM1) and the risk of nonsyndromic cleft lip with or without cleft palate (NSCL/P). The present study aimed to investigate the association between TPM1 polymorphisms and the risk of NSCL/P in an Iranian population. This case‐control was done on 105 NSCL/P patients and 110 unrelated healthy controls. TPM1 rs11071720, rs3803499, rs12148828, and rs1972041 polymorphisms were genotyped by the polymerase chain reaction‐restriction fragment length polymorphism method. The finding showed that rs11071720 polymorphism significantly increased the risk of NSCL/P in homozygous codominant (odds ratio [OR] = 2.54, 95% confidence interval [CI] = 1.14–5.69, p = 0.023, TT vs. CC), recessive (OR = 2.33, 95% CI = 1.06–5.18, p = 0.021, TT vs. CT + CC), and allele (OR = 1.53, 95% CI = 1.02–2.30, p = 0.030, T vs. C). The rs12148828 polymorphism was associated with protection against NSCL/P in codominant (OR = 0.27, 95% CI = 0.15–0.48, p < 0.001, TC vs. TT) and allele (OR = 0.38, 95% CI = 0.22–0.64, p < 0.001, C vs. T). Regarding rs3803499, the findings proposed that this polymorphism significantly increased the risk of NSCL/P in codominant (OR = 3.86, 95% CI = 1.19–12.56, p = 0.025, CC vs. TT) and recessive (OR = 3.74, 95% CI = 1.09–14.15, p = 0.018, CC vs. CT + TT). No significant association was practical between rs1972041 polymorphism and NSCL/P. In conclusion, the findings proposed that TPM1 polymorphisms may contribute to the etiology of NSCL/P in a sample of the Iranian population.     

Polymorphisms in IL‐1A are associated with endometrial cancer susceptibility among Chinese Han population: A case–control study

Endometrial cancer (EC) is one of the most common malignant tumours of the female genital tract, and it has become a serious malignant disease of the female genital tract in China. Existing researches have revealed the association between polymorphisms of IL‐1A and several gynaecological diseases. In this research, we analysed the association between IL‐1A gene polymorphisms and endometrial cancer susceptibility in Chinese female population. A total of 81 patients and 198 healthy people were selected. Odds ratio (OR) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression. Genetic models and analyses showed that IL‐1A rs3783550 TT and rs3783546 CC increased the risk of endometrial cancer under the recessive model, respectively (rs3783550: OR = 2.80, 95%CI: 1.32–5.92, p = .008; rs3783546: OR = 2.79, 95%CI: 1.32–5.89, p = .008). In the recessive model, we also found that both IL‐1A rs1609682 and IL‐1A rs3783521 increased the risk of endometrial cancer, respectively (rs1609682: OR = 2.79, 95%CI: 1.32–5.89, p = .0081; rs3783521: OR = 2.80, 95%CI: 1.32–5.92, p = .008). Haplotype analysis was performed that did not reveal any significant results. In summary, IL‐1A rs3783550, rs3783546, rs1609682 and rs3783521 polymorphisms may be associated with an increased risk of endometrial cancer in Chinese female populations.     

Association of PTPN22 rs2476601 and EGFR rs17337023 Gene polymorphisms and rheumatoid arthritis in Zahedan,Southeast Iran

In this study we aimed to evaluate the possible association of PTPN22 rs2476601 as well as epidermal growth factor receptor (EGFR) rs17337023 gene polymorphism and rheumatoid arthritis (RA) in a sample of Iranian population. This case‐control study was performed on 120 patients with RA and 120 healthy subjects. Genomic DNA was extracted from whole blood and PTPN22 rs2476601 and EGFR rs17337023 polymorphisms were determined using tetra amplification refractory mutation system–polymerase chain reaction (T‐ARMS‐PCR). The results showed that PTPN22 rs2476601 CT genotype as well as rs2476601 T allele was a risk factor for susceptibility to RA (OR=5.89 95%CI = 1.78–19.48, P = 0.004 and OR = 4.78, 95%CI = 1.59–14.35, P = 0.003, respectively). We also found that EGFR rs17337023 AT and rs17337023 TT genotypes were risk factor for susceptibility to RA (OR = 9.94 95%CI = 3.65–26.73, P < 0.001 and OR = 3.66, 95%CI = 1.46–9.15, P = 0.005, respectively). In addition the EGFR rs17337023 T allele was a risk for predisposition to RA (OR = 1.56, 95%CI=1.06‐2.30, P = 0.030). In conclusion, we found an association between PTPN22 rs2476601 and EGFR rs17337023 polymorphisms and the risk of RA in a sample of Iranian population.     

Genetic polymorphism of human leucocyte antigen and susceptibility to multidrug‐resistant and rifampicin‐resistant tuberculosis in Han Chinese from Hubei Province

We determined the high‐resolution allele and haplotype frequencies at the human leucocyte antigen (HLA)A, B and DRB1 loci in the Han population of Hubei province, the TB endemic area of Central China, with pulmonary tuberculosis (PTB), and established the relationship between HLA‐A, B and DRB1 alleles as well as haplotypes and susceptibility to multidrug‐resistant and rifampicin‐resistant tuberculosis (MDR/RR‐TB). Blood samples were drawn from 174 patients with MDR/RR‐TB and 838 patients with drug‐susceptible PTB in ethnic Han population from Hubei province (central China). Four‐digit allele genotyping of HLA‐ A, B and DRB1 loci was performed using polymerase chain reaction with sequence‐specific oligonucleotide probes (PCR‐ SSOP). The allele and haplotype frequencies of HLA‐A, B and DRB1 were determined and compared between patients with MDR/RR‐TB and patients with drug‐susceptible PTB. Statistical analysis of the generated data indicated no departure from expectation of Hardy–Weinberg equilibrium (HWE) at all loci of the control group. Multivariate analysis identified allele DRB1*08:01 (p < .0001; OR = 174.5, 95% CI 15.3–1987.2) as independent predictor of MDR/RR‐TB, except for old age (p < .0001; OR = 10. 9, 95% CI 7.6–15.8), previous treatment history (p < .0001; OR = 11.0, 95% CI 7.2–16.7) and poor compliance to treatment (p < .0001; OR = 12.9, 95% CI 8.4–20.0). While in the subgroup of new TB cases, DRB1*08:01 (p < .0001; OR = 80.3, 95% CI 7.0–917.1) and older age (p < .0001; OR = 3.9, 95% CI 2.4–6.4) were independent susceptibility factors for primary MDR/RR‐TB. Our results suggest that a combination of clinical and host genetic information about tuberculosis patients may contribute to prediction and early detection of MDR/RR‐TB.     

Prospective association between food sensitization and food allergy: results of the LISA birth cohort study

Background Food allergy is common, especially in childhood, where 6–8% of children are affected. Identification of early and efficient markers for later development of food allergy is very important. Objective We examined the ability of repeated measurements of food sensitization in early childhood to predict doctor‐diagnosed food allergy (DDFA) at the age of 6 years. Methods The analysis was based on data from a prospective birth cohort study. Information was collected by parental questionnaires, and blood samples were obtained at 2 and 6 years of age. Children with repeated determination of sensitization to food allergens at 2 and 6 years of age were categorized into the sensitization phenotypes: no, early onset, late onset and persistent sensitization. The association between sensitization phenotypes and DDFA was prospectively investigated using multiple logistic regression analyses. Results Of 3097 children recruited at birth, a complete follow‐up of IgE measurements and questionnaires at 1.5, 2 and 6 years were available for 1082 children. Early food allergen sensitization (fx5) was a strong risk for DDFA at 6 years [odds ratio (OR)=4.7; 95% confidence intervals (95% CI) 2.0–11.2] and for a new onset of DDFA at 6 years (OR=4.1; 95% CI 1.5–11.3). Additionally, persistent food allergen sensitization increased the risk of DDFA at 6 years (OR=6.1; 95% CI 2.7–13.7). Early sensitized children with a history of parental atopy showed the highest risk for DDFA at 6 years. Conclusion Food‐sensitized children during the first 2 years of life, especially with a family history of atopy, might be considered as a susceptible subgroup that requires specific attention concerning the development of food allergy‐related symptoms. >Cite this as: E. Schnabel, S. Sausenthaler, B. Schaaf, T. Schäfer, I. Lehmann, H. Behrendt, O. Herbarth, M. Borte, U. Krämer, A. von Berg, H.‐E. Wichmann, J. Heinrich, and for the LISA Study Group, Clinical & Experimental Allergy, 2010 (40) 450–457.     

Multiplexed immunoglobulin E sensitization in relation to exhaled nitric oxide in a population sample of children

This study investigated the relationship between the specific immunoglobulin E (IgE) profile for 40 allergens using a novel microarray technique (BioIC) and fraction of exhaled nitric oxide (FeNO) in a population sample of 1321 children. Significant positive associations were found between FeNO and sensitization to mites (P < 0.001), animals (P = 0.001), cockroaches (P < 0.001), and foods (P = 0.042), and furthermore, between FeNO and the number of sensitizations (all P < 0.05) or the sum of specific IgE (all P ≤ 0.01) against the aforementioned allergen categories. Specifically, sensitization to the following allergens was significantly related to higher FeNO: Dermatophagoides pteronyssinus, Dermatophagoides farina, Blomia tropicalis, cat, German cockroach, Oriental cockroach, codfish, crab, shrimp, and cheese (all P ≤ 0.01). In conclusion, IgE sensitization to mites, pets, cockroaches, seafood, and cheese, respectively, is significantly associated with elevated FeNO levels in a dose‐dependent fashion in children. Our results provide new evidence that sensitization to certain food allergens may contribute to prompt inflammation in the airways.     

Association of ABCG2 polymorphisms with ischemic stroke in a Chinese population

ATP‐binding cassette, superfamily G, member 2 (ABCG₂) has been shown to play an important role in the development of ischemic stroke in European and African American populations. The aim of the present study is to test the hypothesis that there are associations between ABCG₂ polymorphisms and ischemic stroke risk in a Chinese population. We conducted a case–control study including 967 participants with ischemic stroke and 939 stroke‐free controls. The rs2231137C > T and rs2231142G > T were genotyped using a TaqMan real‐time polymerase chain reaction assay. We found the rs2231137C > T and rs2231142G > T in ABCG₂ were significantly associated with ischemic stroke (sex‐, age‐, BMI‐, SBP‐, DBP‐adjusted OR = 1.252; 95% CI, 1.035–1.515; P‐value = 0.021 and OR = 1.526; 95% CI, 1.085–2.146; P‐value = 0.015, respectively). By haplotype analyses, the haplotype T‐G still had a strongly significant association with ischemic stroke (OR = 0.806; 95% CI, 0.692–0.939; P‐value = 0.00568). Our findings identified the rs2231137C > T and rs2231142G > T polymorphisms of the ABCG₂ as risk factors for ischemic stroke in a Chinese population.     

Increasing trend in atopy markers prevalence in a Croatian adult population between 1985 and 1999

Background Reports about the increasing prevalence of atopy and atopic diseases are common, but recently they have been critically reviewed and the need for relevant research methods has been established. Objectives This study evaluated a 15‐year trend in the prevalence of atopy markers [elevated total IgE, positive skin prick test (SPT) to common aeroallergens and positive atopic symptoms] in Croatian adults, separately for women and men. Methods The study included 721 subjects (445 men and 276 women), 18–45 years old, examined for allergies within a pre‐employment preventive examination. All subjects underwent medical history, SPT with common inhalatory allergens and total serum IgE measurement. The trend analysis of atopy prevalence was performed after stratification of subjects into three consecutive 5‐year periods from 1985 to1999. Results The prevalence of concurrently elevated total IgE and positive atopic symptoms significantly increased during the studied period in men [odds ratio (OR) 2.44, 95% confidence interval (CI) 1.39–4.29, P=0.002]. Women showed an increased prevalence of positive SPT only, with borderline significance (OR 1.65, 95% CI 1.00–2.71, P=0.050). In women, rural residence was found to be a predictor of elevated total IgE (OR 5.36, 95% CI 2.41–11.93, P=0.000) and smoking to be a predictor of concurrently elevated total IgE and positive SPT (OR 6.20, 95% CI 1.67–23.07, P=0.006). Conclusions An increasing trend in the prevalence of concurrently elevated total IgE and positive atopic symptoms was found in the Croatian adult male population between 1985 and 1999, but not in the female population. Sex differences responsible for the production and regulation of IgE were suggested.     

Position paper of the EAACI: food allergy due to immunological cross‐reactions with common inhalant allergens

In older children, adolescents, and adults, a substantial part of all IgE‐mediated food allergies is caused by cross‐reacting allergenic structures shared by inhalants and foods. IgE stimulated by a cross‐reactive inhalant allergen can result in diverse patterns of allergic reactions to various foods. Local, mild, or severe systemic reactions may occur already after the first consumption of a food containing a cross‐reactive allergen. In clinical practice, clinically relevant sensitizations are elucidated by skin prick testing or by the determination of specific IgE in vitro. Component‐resolved diagnosis may help to reach a diagnosis and may predict the risk of a systemic reaction. Allergy needs to be confirmed in cases of unclear history by oral challenge tests. The therapeutic potential of allergen immunotherapy with inhalant allergens in pollen‐related food allergy is not clear, and more placebo‐controlled studies are needed. As we are facing an increasing incidence of pollen allergies, a shift in sensitization patterns and changes in nutritional habits, and the occurrence of new, so far unknown allergies due to cross‐reactions are expected.     

Prevalence of immunoglobulin E-mediated food allergy in 6–9-year-old urban schoolchildren in the eastern Black Sea region of Turkey

Background The prevalence of adverse reactions to food in childhood in Turkey is not known. Objective We aimed to investigate the prevalence and characteristics of IgE‐mediated food allergies (FAs) in 6–9‐year‐old urban schoolchildren. Methods This cross‐sectional study recruited 3500 of the randomly selected 6–9‐year‐old urban schoolchildren from the eastern Black Sea region of Turkey during 2006. Following a self‐administered questionnaire completed by the parents and the child, consenting children were invited for skin prick tests (SPTs) and oral food challenges. Children with suspected IgE‐mediated FA were skin prick tested with a predefined panel of food allergens (milk, hen's egg, soy, wheat, peanut, fish, and hazelnut), aeroallergens (Dermatophagoides pteronyssinus, Dermatophagoides farinae, cat, dog, Alternaria, grass pollen mix, weed pollen mix, and tree pollen mix), and food allergens reported in the questionnaire. All children with a positive SPT to any food were invited for a double‐blind, placebo‐controlled food challenge (DBPCFC). The prevalence of IgE‐mediated FA was established using DBPCFCs. Results The response rate to the questionnaire was 78.2% (2739/3500). The estimated prevalence of parental‐reported IgE‐mediated FA was 5.7% (156/2739) [95% confidence interval (CI), 4.83–6.57%]. The rate of sensitization to the food allergens was 33.1% (48/145) in the parental‐reported group. The confirmed prevalence of IgE‐mediated FA by means of DBPCFC in 6–9‐year‐old urban schoolchildren living in the eastern Black Sea region of Turkey was 0.80% (22/2739) (95% CI, 0.47–1.13%). The most common allergenic foods were beef (31.8%), cow's milk (18.1%), cocoa (18.1%), hen's egg (13.6%), and kiwi (13.6%). Conclusions The rate of reported IgE‐mediated FA was significantly higher than clinically confirmed FA by means of DBPCFC (odds ratio, 7.46; 95% CI, 4.67–12.01; P<0.0001). The order of allergenic foods was different and somewhat unique to the eastern Black Sea region of Turkey when compared with western countries.     

Single‐nucleotide polymorphisms of IRF8 gene are associated with systemic lupus erythematosus in Chinese Han population

Interferon regulatory factor 8 (IRF8) has been shown to have diverse roles in the regulation of the immune system. Two recent studies had revealed the association between the single‐nucleotide polymorphisms (SNPs; rs11644034 and rs2280381) of IRF8 and systemic lupus erythematosus (SLE) in a multiethnic population. The purpose of this study was to evaluate whether the association could be replicated in a Chinese Han population. Genotypes were determined by a multiplex polymerase chain reaction–ligase detection reaction (PCR–LDR) in 358 patients and 357 geographically matched healthy controls. Significant differences in genotype frequency were found between SLE and control individuals (rs11644034: AA vs. GG, P = 0.014, odds ratio (OR) = 0.980, 95% confidence internal (CI): 0.964–0.996; rs2280381: CC vs. TT, P = 0.005, OR = 0.150, 95% CI: 0.033–0.676). Conditional logistic regression analysis showed that the association of rs2280381 remained significant (P adjusted = 0.028) after adjustment for rs11644034, but not vice versa (P adjusted = 0.361).When stratifying patients with SLE according to clinical subtypes, SNP rs2280381 was found to be associated with low complement in patients with SLE. However, SNP rs11644034 was not found to be associated with SLE clinical subgroups. Analysis of the haplotypes revealed that haplotype G‐T and G‐C were also significantly associated with SLE (P = 0.002 and P = 0.012, respectively). Our study indicated that the IRF8 gene polymorphisms might be associated with susceptibility to SLE and with disease‐related clinical manifestations in Chinese Han population.     

Clonorchis sinensis infection is positively associated with atopy in endemic area

Background Epidemiologic studies have suggested that helminth infections play a protective role against allergy; this inverse association, however, has not been consistent. Clonorchis sinensis, the liver fluke of human, is prevalent in the Far East. The association between C. sinensis infection and allergy has not yet been reported. Objective We evaluated the association between clonorchiasis and atopy or allergic diseases in adults in endemic areas of clonorchiasis. Methods A total of 1116 subjects (males 419, females 697; age range, 30–86; mean age=61 years) were recruited from two endemic areas of C. sinensis in Korea. Clonorchiasis was confirmed by stool examination. Allergic symptoms were evaluated with a modified ISAAC questionnaire, and atopy was defined by skin prick test for common inhalant allergens. Total serum IgE and C. sinensis‐specific IgE level was measured by ELISA and methacholine bronchial provocation test was performed to evaluate airway hyperresponsiveness (AHR). Results Clonorchiasis was positively associated with atopy [odds ratio (OR), 1.856; 95% confidence interval (CI), 1.199–2.873] and high levels of total serum IgE (OR, 1.455; 95% CI, 1.050–2.016). Higher association with clonorchiasis was shown in subjects who showed both atopy and high total serum IgE levels (OR, 2.540; 95% CI, 1.448–4.455). Clonorchiasis had no association with wheezing, AHR, asthma or allergic rhinitis. Conclusion and Clinical Relevance Clonorchiasis was positively associated with atopy in adults in endemic area. Cite this as: M‐H Choi, Y‐S Chang, M. K. Lim, Y. M. Bae, S‐T Hong, J‐K Oh, E. H. Yun, M‐J Bae, H‐S Kwon, S‐M Lee, H‐W Park, K‐U Min, Y‐Y Kim and S‐H Cho, Clinical & Experimental Allergy, 2011 (41) 697–705.     

The level of thymic stromal lymphopoietin and its gene polymorphism are associated with rheumatoid arthritis

ObjectiveTo study the correlation between TSLP gene SNPs and RA in a Han Chinese population.MethodsThe genotypes of TSLP genes rs11466749, rs11466750 and rs10073816 among 197 RA patients and 197 controls were analysed by direct sequencing. ELISA was used to detect the plasma TSLP level. Logistic regression analysis was also conducted to identify risk factors for RA.ResultsThe rs11466749 locus GG genotype (OR = 5.30, 95% CI: 1.76–15.95, P < 0.01), dominant model (OR = 1.68, 95% CI: 1.03–2.73, P = 0.04), recessive model (OR = 5.15, 95% CI: 1.72–15.43, P < 0.01), and G allele (OR = 2.02, 95% CI: 1.33–3.09, P < 0.01) were associated with an increased risk of RA. The rs1073816 locus AA genotype (OR = 4.58, 95% CI: 1.49–14.01, P < 0.01), dominant model (OR = 1.75, 95% CI: 1.09–2.79, P = 0.03), recessive model (OR = 4.27, 95% CI: 1.40–13.00, P = 0.03) and A allele (OR = 1.94, 95% CI: 1.29–2.91, P < 0.01) were associated with an increased risk of RA. The rs1073816 locus GA genotype (OR = 0.29, 95% CI: 0.18–0.45, P < 0.01), dominant model (OR = 0.32, 95% CI: 0.21–0.49, P < 0.01) and A allele (OR = 0.45, 95% CI: 0.32–0.63, P < 0.01) were related to a decreased risk of RA susceptibility. The rs1466749 locus GG genotype, rs11466750 AA genotype, and rs10073816 GG genotype were independent risk factors for RA (P < 0.05). The AUC of plasma TSLP level in the diagnosis of RA was 0.8661 (95% CI: 0.8301–0.9002, P < 0.001). There were statistically significant differences in plasma TSLP levels among subjects with different genotypes at rs11466749, rs11466750, and rs10073816 in the TSLP gene (P < 0.05).ConclusionPlasma TSLP levels are a potential molecular marker of RA. SNPs at rs11466749, rs11466750 and rs10073816 of the TSLP gene are related to the susceptibility of the Han Chinese population to RA.     

Risk factors of adverse reactions to food in German adults

Background Allergic diseases have been increasing during the last decades. Previous studies suggest an impact of a variety of risk factors on the prevalence of food hypersensitivity. Objective Data of a cross‐sectional population‐based survey were analysed to study the prevalence of food hypersensitivity in females and males adjusted for age and education. Methods A population aged 18–79 years from a representative, randomly sampled survey studying 13 300 inhabitants from Germany (Berlin) was analysed. The Berlin study data were weighted with regard to age, sex, education and allergic diseases such as atopic dermatitis, rhinoconjunctivitis and asthma. Instruments for evaluation included mailed questionnaires, structured telephone interviews, physical examinations, detection of total IgE, skin prick tests and double‐blind, placebo‐controlled food challenge tests (DBPCFC). Results Three thousand two hundred and twenty‐seven questionnaires were evaluated. The data show a significantly higher risk of self‐reported symptoms in the female group, among persons with higher education and in the age group of 18–39 years. Among individuals with clinical symptoms, females were at lower risk of having positive skin prick tests [aOR=0.32; 95% CI (0.21–0.50); P<0.01] and having a raised total IgE [aOR=0.37; 95% CI (0.24–0.56); P<0.01], but showed a higher risk of non‐IgE and IgE‐mediated food hypersensitivity [aOR=2.27; 95% CI (1.31–3.93); P<0.01] than males. Based on weighted data, the point prevalence of adverse reactions to food resulted in 3.3% [95% CI (2.4–4.5%)] for women and 1.8% [95% CI (1.2–2.7%)] for men after DBPCFC. Conclusion From a general population survey conducted in Germany, we determined that women are at greater risk of having symptoms of food allergy and also at greater risk of having DBPCFC‐confirmed symptomatic food allergy. However, among individuals with symptoms of food allergy, men have a higher prevalence of food‐specific IgE‐sensitization and of raised total IgE than women.     

Changes in cat specific IgE and IgG antibodies with decreased cat exposure

BackgroundCurrent understanding of the effects of reducing exposure to cat allergens is limited. It has also become clear that there are different forms of immune response to cat allergens.ObjectiveTo investigate changes in skin tests and cat specific IgG and IgE antibodies when students from a home with a cat move to a college dormitory.MethodsNinety-seven college students participated in a prospective study that consisted of allergy skin prick testing and serum measurement of IgE and IgG antibodies to cat at the beginning and end of one academic year in college. A subgroup returned for follow-up at the end of 2 years.ResultsAmong 97 students, 33% had IgG antibodies to Fel d 1 but no evidence of sensitization, 25% had positive skin test results and/or serum IgE antibodies, and 42% had negative skin test results and no detectable serum antibodies. Among the non–cat sensitized students with IgG antibodies, the titers decreased during 8 months (P = .002). Titers of IgG4 to Fel d 1 also decreased (P < .001). Among the sensitized students, no change in IgE antibodies to cat occurred in 8 months (P = .20), whereas Fel d 1 specific IgG antibodies decreased (P < .001). Thus, ratios of IgG to IgE decreased highly significantly (P = .007). Among the students with negative skin test results who returned for follow-up (n = 56), none developed positive skin test results or serum IgE antibodies.ConclusionUnder conditions of marked decrease in exposure, no participants developed new-onset sensitization. Among the individuals sensitized at study entry, there were major decreases in the ratio of IgG to IgE.