Serum myeloperoxidase concentration in a healthy population:: biological variations, familial resemblance and new genetic polymorphisms

Serum myeloperoxidase concentration in a healthy population:: biological variations, familial resemblance and new genetic polymorphisms
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DOI:
10.1038/sj.ejhg.5200702
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发表时间:
2001-10-01
影响因子:
5.2
通讯作者:
Visvikis, S
Visvikis, S
中科院分区:
生物学2区
文献类型:
--
作者:
Hoy, A;Trégouët, D;Visvikis, S

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髓过氧化物酶(MPO)通过过量产生活性氧(ROS)及其遗传多态性参与多种疾病的发病机制。本研究的目的是确定影响MPO血清浓度的因素,研究MPO水平的家族相似性,并调查新描述的MPO多态性以及G-463 A与健康人群中MPO水平之间的关联。采用酶免疫分析法(EIA)检测STANISLAS队列中82个健康家系的血清MPO浓度,采用PCR-限制性片段长度多态性或等位基因特异性寡核苷酸分析法检测MPO基因型。MPO浓度显着高于父母比后代。影响MPO水平的因素有年龄、白色细胞数、父亲吸烟和母亲口服避孕药。它们分别解释了男性和女性MPO变异性的12.4%至35.9%。MPO浓度的家庭相关性是相似的幅度。一个新发现的G-129 A置换的-129A等位基因与MPO水平降低显著相关,而-463A等位基因则与血脂变量水平升高相关。在这项研究中,我们确定了影响MPO血清浓度的因素,并表明该基因的分子变异对MPO变异性只有微弱的影响。相反,G-463 A多态性和血脂水平之间的关联可能表明MPO与心血管疾病的风险有关。这些结果必须得到证实,并将以这种方式进行进一步的调查。
Myeloperoxidase (MPO) has been involved in the pathogenesis of several diseases through excessive production of reactive oxygen species (ROS) as well as through its genetic polymorphism. The aims of this study were to identify the factors affecting MPO serum concentration, to study the familial resemblance of MPO levels and to investigate the association between newly described MPO polymorphisms as well as the G-463A one and MPO levels in a healthy population. MPO serum concentrations were measured by an enzymatic immuno-assay (EIA) in 82 healthy families of the STANISLAS Cohort and MPO genotype, determination was performed using PCR-restriction fragment length polymorphism or allele specific oligonucleotide assay. MPO concentrations were significantly higher in parents than in offspring. The factors affecting MPO levels were age, the number of white cells, smoking in fathers and oral contraceptive intake in mothers. They explain from 12.4% up to 35.9% of MPO variability in men and women, respectively. Family correlations of MPO concentrations were of similar magnitude. The -129A allele of a newly described G-129A substitution was significantly associated with decreased MPO levels, whereas the -463A allele was suggested to be associated with increased levels of lipid variables. In this study, we identified factors affecting MPO serum concentrations and showed that molecular variations of the gene have only a weak influence on MPO variability. In contrast, the association between the G-463A polymorphism and lipid levels would suggest a possible implication of MPO in the risk of cardiovascular diseases. These results have to be confirmed and further investigations will be conducted in that way.