Szalai Renata, Matyas Petra, Varszegi Dalma, Melegh Marton, Magyari Lili, Jaromi Luca, Sumegi Katalin, Duga Balazs, Kovesdi Erzsebet, Hadzsiev Kinga, Melegh Bela
Department of Medical Genetics, University of Pecs, Szigeti 12, Pecs, 7624, Hungary.
Mol Biol Rep. 2014 Nov;41(11):7665-9. doi: 10.1007/s11033-014-3659-7. Epub 2014 Aug 5.
Variants of glucocorticoid induced transcript 1 (GLCCI1) result decreased response to inhaled corticosteroids, while intronic variant of low-affinity IgE receptor (FCER2) is associated with exacerbation rates in children with asthma. We examined the ethnic differences, allele and genotype frequencies of two linked single nucleotide polymorphisms (rs37972, rs37973) of GLCCI1 and rs28364072 intronic variant of FCER2 gene in average Roma and Hungarian population. A study population of 474 healthy Roma and 397 Hungarian subjects were characterized for GLCCI1 and FCER2 polymorphisms using real time polymerase chain reaction (PCR) assay and PCR-restriction fragment length polymorphism method. The rs37972 and rs37973 polymorphisms in GLCCI1 were found in 100% linkage disequilibrium both in Romas and in Hungarians. We found significant differences between the two groups regarding both minor allele frequencies (54.5 vs. 43.8%, p ≤ 0.01) and homozygous genotype (31.6 vs. 21.3%, p ≤ 0.01) of GLCCI1. For FCER2 rs28364072 the homozygous variant genotype was present in 2.8% in Romas, while in Hungarians it was 5.8% (p = 0.032). The opposite changes of these two polymorphisms strongly suggest that contrary current belief analyses of GLCCI1 variants are insufficient for personalised glucocorticoid therapies in different populations.
糖皮质激素诱导转录本1(GLCCI1)的变异会导致对吸入性糖皮质激素的反应降低,而低亲和力IgE受体(FCER2)的内含子变异与哮喘患儿的病情加重率相关。我们研究了罗姆族和匈牙利族普通人群中GLCCI1的两个连锁单核苷酸多态性(rs37972、rs37973)以及FCER2基因的rs28364072内含子变异的种族差异、等位基因和基因型频率。使用实时聚合酶链反应(PCR)分析和PCR-限制性片段长度多态性方法,对474名健康罗姆人和397名匈牙利受试者的研究群体进行GLCCI1和FCER2多态性特征分析。在罗姆人和匈牙利人中,GLCCI1的rs37972和rs37973多态性均处于100%连锁不平衡状态。我们发现两组在GLCCI1的次要等位基因频率(54.5%对43.8%,p≤0.01)和纯合基因型(31.6%对21.3%,p≤0.01)方面均存在显著差异。对于FCER2的rs28364072,纯合变异基因型在罗姆人中的比例为2.8%,而在匈牙利人中为5.8%(p = 0.032)。这两种多态性的相反变化强烈表明,与当前观点相反,对GLCCI1变异的分析不足以用于不同人群的个性化糖皮质激素治疗。