Haarala Atte, Eklund Carita, Pessi Tanja, Lehtimäki Terho, Huupponen Risto, Jula Antti, Viikari Jorma, Raitakari Olli, Hurme Mikko
Department of Microbiology and Immunology, University of Tampere, Tampere, Finland.
Scand J Clin Lab Invest. 2009;69(2):168-74. doi: 10.1080/00365510802449642.
Use of combined oral contraceptives (COCs) is known to increase concentrations of C-reactive protein (CRP), an important predictor of cardiovascular disease. The inflammatory nature of the disease is well acknowledged. The aim of this study was to find out whether the metabolic, lifestyle and genetic determinants of CRP differ between women who use COCs and those who do not use any hormonal contraceptives (non-users).
A total of 1,257 women (24-39 years) participated in the ongoing Cardiovascular Risk in Young Finns Study, a population based cross-sectional follow-up study. Use of hormonal contraceptives was determined by questionnaire. Plasma CRP and other cardiovascular risk factors were measured; five CRP gene polymorphisms were genotyped (-717A>G, -286C>T>A, +1059G>C, +1444C>T and +1846G>A) and CRP haplotypes were constructed.
Multivariate regression analysis revealed that BMI and leptin were the main determinants of CRP in non-users, whereas in COC users the main determinants were BMI, leptin and triglycerides. The median CRP and triglyceride values were significantly higher in COC users than in non-users. The correlations between triglyceride and CRP were tested separately in different COC users in accordance with progestagen content and dosage, the analysis revealing significant association only in women using a high dosage of progestagen or cyproterone. The haplotypes of CRP gene had no significant association with CRP concentration in COC users, while independent effects on CRP were found in non-users.
Our study suggests that use of COCs alters the metabolic determinants and genetic regulation of CRP.
已知使用复方口服避孕药（COC）会增加C反应蛋白（CRP）的浓度，CRP是心血管疾病的一项重要预测指标。该疾病的炎症性质已得到充分认可。本研究的目的是查明使用COC的女性与未使用任何激素避孕药（非使用者）的女性在CRP的代谢、生活方式和遗传决定因素方面是否存在差异。
共有1257名年龄在24至39岁之间的女性参与了正在进行的芬兰年轻人心血管风险研究，这是一项基于人群的横断面随访研究。通过问卷调查确定激素避孕药的使用情况。测量血浆CRP和其他心血管危险因素；对五个CRP基因多态性进行基因分型（-717A>G、-286C>T>A、+1059G>C、+1444C>T和+1846G>A）并构建CRP单倍型。
多变量回归分析显示，体重指数（BMI）和瘦素是未使用者中CRP的主要决定因素，而在使用COC的女性中，主要决定因素是BMI、瘦素和甘油三酯。使用COC的女性的CRP和甘油三酯中位数显著高于未使用者。根据孕激素含量和剂量，在不同的COC使用者中分别测试甘油三酯与CRP之间的相关性，分析显示仅在使用高剂量孕激素或环丙孕酮的女性中存在显著关联。CRP基因的单倍型与使用COC的女性的CRP浓度无显著关联，而在未使用者中发现对CRP有独立影响。
我们的研究表明，使用COC会改变CRP的代谢决定因素和基因调控。
