Interleukin-4 rs2243250 polymorphism is associated with asthma among Caucasians and related to atopic asthma

Published data on the association between interleukin-4 (IL-4) rs2243250 (C-589T) polymorphism and asthma susceptibility are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. A total of 17 studies with 3037 asthma patients and 3032 healthy controls were included. Overall, significantly elevated asthma risk was associated with IL-4 T allele when all studies were pooled into the meta-analysis (CT vs. CC: OR=1.187, 95% CI=1.016-1.387; dominant model: OR=1.213, 95% CI=1.046-1.405). In the subgroup analysis by ethnicity, significantly increased risk was only found for Caucasians (TT vs. CC: OR=1.591, 95% CI=1.032-2.452; dominant model: OR=1.292, 95% CI=1.028-1.624). When stratified by asthma type, statistically significantly elevated risk was only found in atopic asthma group (dominant model: OR=1.313, 95% CI=1.033-1.667). Despite some limitations, this meta-analysis suggests that T allele at position -589 of the IL-4 gene promoter region is a low-penetrant risk factor for asthma development especially for Caucasians and atopic type.     

Montelukast in asthma treatment in Croatia

The aim of this study was to determine the efficacy and safety of montelukast added to previous medication in the treatment of a mild and moderate asthma. Data were obtained via questionnaires given to the physicians and given further to their patients. Patients were divided in two groups, first followed 4 weeks (612 patients) and second followed 8 weeks (91 patients). We found out that there was a significant improvement in FEV1 (forced expiratory volume in first second) and general condition of patients and decreased number of salbutamol inhalations after using montelukast. In the second group of patients we find out the same significant improvement in FEV1, general condition and decrease in salbutamol inhalations after 4 weeks of using montelukast and further improvement after the next month of therapy. We conclude that montelukast is an efficient drug with little side effects and with a good compliance. Montelukast managed to achieve a good asthma control; therefore it has a significant place in asthma therapy.     

The distribution of rare alleles

Population geneticists have long been interested in the behavior of rare variants. The definition of a rare variant has been the subject of some debate, centered mainly on whether alleles with small relative frequency should be considered rare, or whether alleles with small numbers should be. We study the behavior of the counts of rare alleles in samples taken from a population genetics model that allows for selection and infinitely-many-alleles mutation structure. We show that in large samples the counts of rare alleles — those represented once, twice, ... — are approximately distributed as a Poisson process, with a parameter that depends on the total mutation rate, but not on the selection parameters. This result is applied to the problem of estimating the fraction of neutral mutations.     

白癜风的HLA等位基因遗传学研究进展

白癜风的病因尚不明,国内外研究表明其发生与遗传因素相关,其遗传特征不符合孟德尔遗传规律,而是属于多基因遗传的范畴.主要与人类白细胞抗原HLA-Ⅰ类、Ⅱ类及Ⅲ类基因及其产物相关,以往文献报道认为HLA-Ⅱ类基因与白癜风的关系最为密切.HLA基因的多态性决定HLA分子的多样性.充分认识HLA基因水平的多态性,有助于白癜风的基因诊断和治疗.     

The characteristics of the distribution of HLA antigens in the families of children with aneuploid chromosomal pathology

Search of possible immunogenetic markers of tendency to form aneuploid offspring was carried out. We have studied HLA-antigens distribution among families with Down syndrome and Turner syndrome children and among families with miscarriages. The disposition to reproduction of affected offspring is associated with following HLA-antigens: B40, B41 and B51. The most typical haplotypes among families with affected offspring were: A2B27, A2B40, A2B51, A9B51, A10B8, A10B40. The HLA-antigens distribution among families with miscarriages supports evidence, that certain haplotypes can contribute to aneuploidy in progeny.     

Polymorphism of interleukins and interleukin receptor genes: population distribution and association with atopic bronchial asthma

Population distribution and pathogenetic significance for bronchial asthma (BA) of the eight polymorphic variants of six interleukin--(IL) and interleukin receptor genes, C-589T, G/C 3'-UTR IL4, C-703T IL5, T113M IL9, Q551R, 150V IL4RA, and G1972A IL5RB, was examined. In the population samples of Russians, Tajiks, Buryats, and Tuvinians racial and ethnic specificity of these polymorphisms was established. These specific features were manifested as population-specific "enetic portraits" in respect of polymorphic allele frequencies. Analysis of the BA patients and their relatives from Tomsk by use of transmission/disequilibrium test (TDT) revealed the presence of a statistically significant association between the C-703 IL5 allele and the disease (P = 0.005). This is the first evidence of an association between the IL5 gene polymorphism and BA.     

PCR/oligonucleotide probe typing of HLA class II alleles in a Filipino population reveals an unusual distribution of HLA haplotypes.

We have analyzed the distribution of HLA class II alleles and haplotypes in a Filipino population by PCR amplification of the DRB1, DQB1, and DPB1 second-exon sequences from buccal swabs obtained from 124 family members and 53 unrelated individuals. The amplified DNA was typed by using nonradioactive sequence-specific oligonucleotide probes. Twenty-two different DRB1 alleles, including the novel Filipino *1105, and 46 different DRB1/DQB1 haplotypes, including the unusual DRB1*0405-DQB1*0503, were identified. An unusually high frequency (f = .383) of DPB1*0101, a rare allele in other Asian populations, was also observed. In addition, an unusual distribution of DRB1 alleles and haplotypes was seen in this population, with DR2 (f = .415) and DRB1*1502-DQB1*0502 (f = .233) present at high frequencies. This distribution of DRB1 alleles differs from the typical HLA population distribution, in which the allele frequencies are more evenly balanced. The distribution of HLA class II alleles and haplotypes in this Filipino population is different from that of other Asian and Pacific groups: of those populations studied to date; the Indonesian population is the most similar. DRB1*1502-DQB1*0502 was in strong linkage disequilibrium (D'' = .41) with DPB1*0101 (f = .126, for the extended haplotype), which is consistent with selection for this DR, DQ, DP haplotype being responsible for the high frequency of these three class II alleles in this population.     

Association of HLA class I antigens and HLA class II alleles with vitiligo in a Turkish population

As is the case with many other autoimmune diseases, there is an association between vitiligo and HLA complex. HLA subtypes vary with racial/ethnic background. The purpose of this study was to determine which HLA class I antigens and HLA class II alleles are associated with Turkish vitiligo patients. Forty-one patients with vitiligo and 61 healthy control subjects were typed for HLA class II alleles. Thirty-three out of 41 patients with vitiligo and 100 healthy transplant donors were typed for HLA class I antigens. HLA DNA typing was performed by polymerase chain reaction/sequence specific primer method for class II. HLA typing for class I was performed by serological method. The frequency of HLA DRB1*03 was 0.6340 in patients compared to 0.2950 in controls (P = 0.0014). The frequency of HLA DRB1*04 was found to be 0.6830 in patients compared to 0.2950 in controls (P = 0.00026). The allele HLA DRB1*07 was present in 0.390 of patients compared to 0.0820 of the controls (P = 0.0004). A preventive antigen for the manifestation of vitiligo has not been identified in this study. Our findings suggest that DRB1*03, DRB1*04 and DRB1*07 alleles are genetic markers for general susceptibility to vitiligo in a Turkish population.     

Clinical and immunological effect produced by vaccination with "Pneumo 23" of children with atopic bronchial asthma

A total of 45 children aged 4-16 years with atopic bronchial asthma of different severity level-resulted from a past case of outhospital pneumonia, received vaccine "Pneumo 23" ("Aventis Pasteur", France). The vaccine was found to be well tolerated, no cases of the exacerbation of the atopic process were registered. A reliable Increased level of specific antibodies to the mixture of polysaccharides, contained in the vaccine "Pneumo 23", was found to occur. The tendency towards decreased level of serum IgE was established.     

Common HLA alleles associated with health, but not with facial attractiveness

Three adaptive hypotheses have been proposed to explain the link between the human leucocyte antigen (hla) genes, health measures and facial attractiveness: inbreeding avoidance, heterozygote advantage and frequency-dependent selection. This paper reports findings that support a new hypothesis relating HLA to health. We suggest a new method to quantify the level of heterozygosity. HLA heterozygosity did not significantly predict health measures in women, but allele frequency did. Women with more common HLA alleles reported fewer cold and flu bouts per year, fewer illnesses in the previous year and rated themselves healthier than women with rare alleles. To our knowledge, this is the first study to show a positive correlation between HLA allele frequency and general health measures. We propose that certain common HLA alleles confer resistance to prevalent pathogens. Nevertheless, neither HLA heterozygosity nor allele frequency significantly predicted how healthy or attractive men rated the female volunteers. Three non-mutually exclusive explanations are put forward to explain this finding.     

The mycoplasma infection rate in children with bronchial asthma

A total of 167 children with bronchial asthma (BA) have been examined for the mycoplasma infection rate. Among investigated patients 62,8% were infected with one or more mycoplasma species. The prolonged persistence in patient body as well as biological properties of mycoplasmas give grounds to consider these agents as a risk factor in the development of the allergy-infection-borne BA and its relapses.     

HLA class II associations with rheumatic heart disease among clinically homogeneous patients in children in Latvia

Genetic control of immune reactions has a major role in the development of rheumatic heart disease (RHD) and differs between patients with rheumatic fever (RF). Some authors think the risk of acquiring RHD is associated with the HLA class II DR and DQ loci, but other views exist, due to the various HLA-typing methods and ways of grouping cases. Our goal was to determine the relations between HLA class II alleles and risk of or protection from RF in patients with relatively homogeneous clinical manifestations. A total of 70 RF patients under the age of 18 years were surveyed in Latvia. HLA genotyping of DRB1*01 to DRB1*18 and DQB1*0201-202, *0301-305, *0401-402, *0501-504, and *0601-608 was performed using polymerase chain reaction sequence-specific primers. Data for a control group of 100 healthy individuals typed for HLA by the same method were available from the databank of the Immunology Institute of Latvia. Of the RF patients, 47 had RHD and 8 had Sydenham's chorea. We concluded that HLA class II DRB1*07-DQB1*0401-2 and DRB1*07-DQB1*0302 could be the risk alleles and HLA class II DRB1*06 and DQB1*0602-8, the protective ones. Patients with mitral valve regurgitation more often had DRB1*07 and DQB1*0401-2, and patients with multivalvular lesions more often had DRB1*07 and DQB1*0302. In Sydenham's chorea patients, the DQB1*0401-2 allele was more frequent. Genotyping control showed a high risk of RF and RHD in patients with DRB1*01-DQB1*0301-DRB1*07-DQB1*0302 and DRB1*15-DQB1*0302-DRB1*07-DQB1*0303.     

Association of interleukin-13 gene polymorphisms with atopic bronchial asthma

A comparative analysis of allele and genotype distribution of C(−1055)T and R130Q IL13 gene polymorphisms has been performed in Russian patients from the Moscow region. In the study, 283 DNA specimens of atopic bronchial asthma (BA) patients and 227 DNA specimens of healthy donors were used. No association of these markers with atopic BA development as well as with total IgE concentration has been found. Haplotype frequency analysis did not reveal significant difference between samples. However, significant association of C(−1055)T polymorphism with the disease severity has been revealed (OR = 2.39, 95% confidence interval 1.44–3.98, p = 0.001). Therefore, C(−1055)T polymorphism was shown to be associated with atopic BA progression.     

Frequency of HLA alleles in a sample population from Campania

The authors present their findings on the HLA A and B antigens frequent in Campania by means of a 127 random people sample. Only the HLA 1-8 aplotype shows a clear crossing-over disequilibrium.     

HLA class II polymorphism in autochthonous population of Gorski kotar, Croatia

The aim of this study was to examine frequencies and haplotypic associations of HLA class II alleles in autochthonous population of Gorski kotar (Croatia). HLA-DRB1, -DQA1 and -DQB1 alleles were determined by DNA based PCR typing in 63 unrelated inhabitants from Gorski kotar whose parents and ancestors were born and lived in tested area for at least over four generations. A total of 13 HLA-DRB1, 12 DQA1 and 14 DQB1 alleles were identified. The most frequent HLA class II genes in Gorski kotar population are: HLA-DRB1*13 (af = 0.150), -DRB1*03 (af = 0.142), -DRB1*07 (af = 0.119), and -DRB1*11 (af = 0.119), HLA-DQA1*0501 (af = 0.278), -DQA1*0102 (af = 0.183), -DQA1*0201 (af = 0.127) and HLA-DQB1*0301 (af = 0.157), -DQB1*0201 (af = 0.139), -DQB1*0501 (af = 0.111). We have identified 24 HLA class II three-locus haplotypes. The most common haplotypes in Gorski kotar population are DRB1*03-DQA* 0501-DQB1*0201 (0.120), DRB1*11-DQA1*0501-DQB1*0301 (0.111) and DRB1*07-DQA1*0201-DQB1*0202 (0.094). The allelic frequencies and populations distance dendrogram revealed the closest relationships of Gorski kotar population with Slovenians, Germans, Hungarians and general Croatian population, which is the result of turbulent migrations within this microregion during history.     

Growth problems in children with asthma

Growth problems are often seen in children with asthma. Rarely, these problems may be caused by poor asthma control. Negatively-deviating growth curves in asthmatic boys aged 8-15 years are often associated with a chronic delay in growth and puberty. Daily treatment with any dose of systemic corticosteroids suppresses the growth rate for as long as the treatment is maintained. The risk of growth rate suppression due to inhaled corticosteroids depends on the dose, administration regimen and delivery device. The risk becomes significant with > or =800 microg budesonide from a metered-dose inhaler with a spacer, and with > or =400 microg budesonide or fluticasone propionate from a dry-powder inhaler. Regardless of the treatment modality applied, all children with asthma should have their height growth measured at least every 6 months, and indications for endocrine work-up should follow general criteria for a growth-insufficient child.