Polymorphisms in ADAM33 are associated with allergic rhinitis due to Japanese cedar pollen

BACKGROUND: A recent report provided evidence that a disintegrin and metalloprotease domain 33 (ADAM33), a member of the ADAM family, is a novel susceptibility gene in asthma linked to bronchial hyper-responsiveness. However, there has been no investigation of the genetic role of ADAM33 variants in nasal allergy. OBJECTIVE: The purpose of this study was to test the association between ADAM33 polymorphisms and Japanese cedar pollinosis (JCPsis), a most common seasonal allergic rhinitis in Japan. METHODS: We conducted a case-control association study among a Japanese population, involving 95 adult individuals with JCPsis and 95 normal healthy controls. A total of 22 single-nucleotide polymorphisms (SNPs) in ADAM33 were genotyped using PCR-based molecular methods. RESULTS: Six SNPs of ADAM33 gene, three in introns (7575G/A, 9073G/A and 12540C/T) and three in the coding region (10918G/C, 12433T/C and 12462C/T), were strongly associated with JCPsis (P = 0.0002-0.022 for absolute allele frequencies) and most of the SNPs were in linkage disequilibrium with each other. A higher frequency of the common alleles of these SNPs was noted for the subjects with JCPsis in comparison with healthy controls. We also identified a haplotype associated with the disease susceptibility. In addition, associations were found between ADAM33 polymorphisms and various cedar pollinosis phenotypes including clinical severity, eosinophil counts in nasal secretion and allergen-specific IgE levels in sera, but not total serum IgE levels. CONCLUSION: These results indicate that polymorphisms in the ADAM33 gene are associated with susceptibility to allergic rhinitis due to Japanese cedar pollen, but the functional relationship still needs clarification.     

中国南方汉族和苗族人群hPARP1基因遗传多态性

目的检测人类聚腺苷二磷酸核糖聚合酶1[poly（ADP-ribose）polymerase 1，PARP1]基因的基因型和基因频率在中国南方汉族和苗族人群中的分布。方法收集187名中国南方汉族和210名苗族人的血液DNA，用PCR法扩增hPARP1基因4个外显子，并进行单链构象多态性分析。结果用PCR成功扩增出第12、13、16、17外显子，片段长度分别为253bp、313bp、175bp、362bp，在187名中国南方汉族和210名苗族人群中，分别有3人和9人检测出hPARP1基因第12、13、16和17外显子上各有1种基因突变，分别为Phe548Ser、Ala683Ser、Asp798Tyr、His808Arg。结论中国南方汉族和苗族人群中hPARP1基因第12、13、16和17外显子上存在突变型等位基因。     

The impact of GJA3 SNPs on susceptibility to age-related cataract

AIM: To determine the association of gap junction protein alpha 3 (GJA3) gene tag single-nucleotide polymorphisms (SNPs) with susceptibility to age-related cataract (ARC). METHODS: In total, 486 ARC patients were matched with 500 healthy controls. All the participants underwent complete ophthalmic examinations. Haplotype-tagging SNPs of GJA3 gene were selected from the HapMap Beijing Han Chinese population. Genomic DNA was extracted from the peripheral blood leukocytes of all the subjects. Under three different genetic models: dominant, recessive, and additive, the association between SNPs and ARC was examined. After adjusting for age and sex, the genetic effects of the GJA3 SNPs were evaluated with logistic regression analysis. RESULTS: Four tag GJA3 SNPs (rs6490519, rs9506430, rs9509053, and rs9552089) were included in the present study. None of the SNPs showed a significant relationship with an altered risk of total ARC under the dominant, recessive, or additive models. In the subgroup analysis, rs9506430 had a significant effect on the formation of a posterior subcapsular cataract (P=0.002, OR: 0.227, 95%CI: 0.088-0.590) under the recessive model. CONCLUSION: Our study indicates that GJA3 variants may influence the development of posterior subcapsular cataracts. Further studies need to be designed to confirm this possibility.     

Genetic variation associated with chromosomal aberration frequency: A genome-wide association study

Chromosomal aberrations (CAs) in human peripheral blood lymphocytes (PBL) measured with the conventional cytogenetic assay have been used for human biomonitoring of genotoxic exposure for decades. CA frequency in peripheral blood is a marker of cancer susceptibility. Previous studies have shown associations between genetic variants in metabolic pathway, DNA repair and major mitotic checkpoint genes and CAs. We conducted a genome-wide association study on 576 individuals from the Czech Republic and Slovakia followed by a replication in two different sample sets of 482 (replication 1) and 1288 (replication 2) samples. To have a broad look at the genetic susceptibility associated with CA frequency, the sample sets composed of individuals either differentially exposed to smoking, occupational/environmental hazards, or they were untreated cancer patients. Phenotypes were divided into chromosome- and chromatid-type aberrations (CSAs and CTAs, respectively) and total chromosomal aberrations (CAtot). The arbitrary cutoff point between individuals with high and low CA frequency was 2% for CAtot and 1% for CSA and CTA. The data were analyzed using age, sex, occupation/cancer and smoking history as covariates. Altogether 11 loci reached the P-value of 10⁻⁵ in the GWAS. Replication 1 supported the association of rs1383997 (8q13.3) and rs2824215 (21q21.1) in CAtot and rs983889 (5p15.1) in CTA analysis. These loci were found to be associated with genes involved in mitosis, response to environmental and chemical factors and genes involved in syndromes linked to chromosomal abnormalities. Identification of new genetic variants for the frequency of CAs offers prediction tools for cancer risk in future. Environ. Mol. Mutagen. 60:17–28, 2019. © 2018 Wiley Periodicals, Inc.     

A review of potential pharmacogenetic effects on catecholamine responses

Considerably, variability in the clinical response to inotropic agents is observed and could be explained partially by the genetic variants, such as single-nucleotide polymorphism (SNP) in genes encoding for enzymes implicated in catecholamines synthesis, metabolism, storage and release or in the signaling pathway. This review highlights the potential effect of pharmacogenetics studies in hemodynamic response and identified 11 SNPs that could be relevant to explain the high variability drug response for a same dose. Cardiovascular instability, such as hypotension, is one of the premature birth complications. The pharmacogenetics studies evaluating these SNP may be useful to better understand the clinical outcome, particularly in this population.     

Unique features of chicken Toll-like receptors

Toll-like receptors (TLRs) are a major class of innate immune pattern recognition receptors that have a key role in immune homeostasis and the defense against infections. The research explosion that followed the discovery of TLRs more than a decade ago has boosted fundamental knowledge on the function of the immune system and the resistance against disease, providing a rational for clinical modulation of the immune response. In addition, the conserved nature of the ancient TLR system throughout the animal kingdom has enabled a comparative biology approach to understand the evolution, structural architecture, and function of TLRs. In the present review we focus on TLR biology in the avian species, and, especially, on the unique functional properties of the chicken TLR repertoire.     

DNA-SNP等位基因比率分析快速诊断产前唐氏综合征

目的探讨羊水胎儿上皮细胞DNA-单核苷酸多态性(SNP)等位基因比率分析法快速诊断产前唐氏综合征的效果。方法选取产前诊断为21三体单胎妊娠的冻存羊水标本24例及产前诊断为二倍体单胎妊娠的标本76例。利用基质辅助激光吸收离子化时间飞行质谱技术(MALDI-TOF)对位于21号染色体上的一个SNP位点,rs7844进行了杂合度的检测,对杂合子样本进行等位基因比率分析。结果 100例羊水标本中,检出rs7844杂合子样本26例,其中21三体6例,二倍体20例。DNA-SNP等位基因比率分析诊断产前唐氏综合征只需1~2 d,但诊断敏感性可达100%。结论羊水细胞DNA-SNP等位基因比率分析可达到快速诊断产前唐氏综合征的目的。     

斑秃易感位点与中国汉族人群相关性研究

目的：研究国外斑秃人群已发现的易感基因与中国汉族人群斑秃的相关性。方法选择736例斑秃患者和1840例对照者,提取基因组 DNA,利用 Sequenom Massarray系统,对国外报道的斑秃易感基因位点[17个单核苷酸多态性(SNPs)]进行验证,用 Plink 1．07软件对基因型进行关联分析。结果 CTLA4基因上 rs3087243( P =0．041, OR =1．18,95% CI =1．01~1．38),经 Bonferroni 校正后无显著相关性(Pc =0．697),其余16个位点( TLR1、DMBT1、CHIT1、GBP4、 CIITA、 IL31RA、 CD96、 INPPL1、 MASP2、 IL-13、 KI-AA0350、PTPN22、SPATA5、TRAF1/ C5、IL1A、IL2RA)等位基因频率在病例组和对照组之间差异无统计学意义( P >0．05);分层分析显示发病年龄>20岁与≤20岁两组之间比较, TRAF1基因中 rs2416808位点(P =0．0184, OR =1．35,95% CI =1．05~1．74);轻型与重型斑秃、有无家族史,等位基因频率在两两之间比较差异均无统计学意义(P >0．05)。结论国外报道的17个 SNPs 与中国汉族人群的斑秃没有显著相关性,不同人群之间可能存在遗传异质性,进一步的研究需要在较大的斑秃样本中进行。