Association of vitamin D binding protein variants with chronic mucus hypersecretion in Iceland.
Association of vitamin D binding protein variants with chronic mucus hypersecretion in Iceland.
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DOI：
10.2165/00129785-200404010-00007
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发表时间：
2004-01-01
期刊：
影响因子：
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通讯作者：
Hakonarson, Hakon
中科院分区：
文献类型：
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作者：
Laufs, Jurgen;Andrason, Hjalti;Hakonarson, Hakon
背景：以往对维生素D结合蛋白(VDBP，又称群特异性成分，GC，由GC基因编码)的研究表明，GC*2和GC*1F两个基因变体可能分别与慢性阻塞性肺疾病(COPD)的保护和易感性有关。这项研究的目的是研究VDBP与COPD不同亚型的相关性。研究设计：对冰岛COPD患者的各种GC基因型与COPD表型的相关性进行了研究，冰岛大学医院的肺科医生对这些患者进行了跟踪调查。方法：所有患者都进行了GC基因已知等位基因的基因分型。单核苷酸多态(SNPs)采用限制性片段长度多态分析方法进行检测。根据变异的等位基因频率估计研究能力，并通过受影响组中的基因型流行率除以对照人群中的流行率来计算风险比。病例组：102例慢性阻塞性肺疾病患者和183例正常对照，46例哮喘患者和48例慢性粘液高分泌患者。主要结果测量和结果：结果显示，慢性阻塞性肺疾病患者和健康对照组的GC等位基因和基因型频率相似。然而，CMH患者携带GC*1F等位基因的比例高于对照组，而携带GC*2等位基因的比例低于对照组。这种差异在纯合子形式中最为显著：Gc*1F/*1F和Gc*2/*2分别为8.3%和1.1%，0.0%和7.6%。在控制吸烟因素后，只有不吸烟的慢性肥厚性心脏病患者的GC*1F/*1F基因频率发生显著改变(p=0.0001)。伴有气流阻塞的支气管高分泌患者的GC*2/*2基因频率也显著低于对照组(2.9%vs7.6%)。综上所述，这些结果表明，GC*1F和GC*2等位基因与患COPD风险增加的个体的痰高分泌有关。
BACKGROUND: Previous studies of vitamin D binding protein (VDBP, also known as group-specific component, Gc, encoded by the GC gene) have implicated two gene variants, GC*2 and GC*1F, as possible contributors with chronic obstructive pulmonary disease (COPD) protection and susceptibility, respectively. The objective of this study was to examine the association of VDBP to different subtypes of COPD.STUDY DESIGN: The association of the various GC genotypes to the COPD phenotype was examined in Icelandic COPD patients who were followed by pulmonary physicians at the University Hospital of Iceland.METHODS: All patients were genotyped for the known alleles of the GC gene. The single nucleotide polymorphisms (SNPs) were identified by a restriction fragment length polymorphism procedure. Study power was estimated based on allele frequencies of the variants, and risk ratios were calculated from the prevalence of genotypes in the affected group divided by its prevalence in the control population. Statistical analyses were performed using the 2-tailed Fisher's Exact Test and chi(2) test, where appropriate.PATIENT GROUP: One hundred and two COPD patients and 183 controls, together with 46 asthma patients and 48 patients with chronic mucous hypersecretion (CMH) were examined.MAIN OUTCOME MEASURE AND RESULTS: The results demonstrate similar allele and genotype frequencies of GC in COPD patients overall and healthy controls. However, there was a higher prevalence of genotypes carrying a GC*1F allele and lower prevalence of genotypes with a GC*2 allele in the CMH patients than in controls. This difference was most notable in the homozygous form: 8.3% vs 1.1% for the GC*1F/*1F, and 0.0% vs 7.6% for the GC*2/*2 genotypes, respectively. When controlled for smoking, only the non-smoking CMH patients demonstrated a significantly altered frequency of the GC*1F/*1F genotype (p = 0.0001). The prevalence of the GC*2/*2 genotype was also significantly lower in patients with bronchial hypersecretion with airflow obstruction compared with the control group (2.9% vs 7.6%). Taken together, these results demonstrate that the GC*1F and GC*2 alleles are associated with sputum hypersecretion in individuals who are at increased risk of developing COPD.