The 312N variant of the luteinizing hormone/choriogonadotropin receptor gene (LHCGR) confers up to 2•7-fold increased risk of polycystic ovary syndrome in a Sardinian population
The 312N variant of the luteinizing hormone/choriogonadotropin receptor gene (LHCGR) confers up to 2•7-fold increased risk of polycystic ovary syndrome in a Sardinian population
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DOI：
10.1111/j.1365-2265.2012.04372.x
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发表时间：
2012-07-01
影响因子：
3.2
通讯作者：
Tiziano, F. D.
中科院分区：
文献类型：
--
作者：
Capalbo, A.;Sagnella, F.;Tiziano, F. D.
多囊卵巢综合征（PCOS）是一种常见的疾病，约有15%的育龄妇女患有PCOS。由于其家族发生，一个多因素的易感性模型，包括遗传和环境因素，已被提出。然而，遗传因素的识别一直难以捉摸。设计：病例对照研究，旨在评估促黄体生成素/绒毛膜促性腺激素受体基因（LHCGR）功能相关变异体与PCOS表型之间可能的关联。患者共198例PCOS和187例非PCOS妇女，年龄1435岁，撒丁岛的起源，被称为妇产科的卡利亚里大学（撒丁岛）的门诊部。PCOS的诊断是基于鹿特丹标准。我们确定了LHCGR基因座上ins 18 LQ、S291 N和S312 N变体的基因型。基因型与多囊卵巢综合征的存在或不存在以及几个临床和生化特征有关。结果312 N等位基因与PCOS的发生密切相关（OR为2.04; 95% CI为1.323.14;？2，10.47; P = 0.001）。312 N纯合性与进一步的风险增加相关（OR，2.73; 95%CI，1.255.95;？2，6.65; P = 0.01）。在对照组中，ins 18 LQ等位基因的数量与LH血清水平相关（？2，8.04，P = 0.017）。结论：我们首次在一个孤立的人群中发现了一种与PCOS密切相关的遗传变异。这些结果，如果在其他队列中得到证实，可能会提供机会，以测试在LHCGR基因座的S312 N基因型在生育妇女，以评估PCOS的风险。避免体重增加等触发因素可能会改善潜在风险受试者的生殖结局。
Objective Polycystic ovary syndrome (PCOS) is a frequent condition, affecting about 15% of women of reproductive age. Because of its familial occurrence, a multifactorial model of susceptibility, including both genetic and environmental factors, has been proposed. However, the identification of genetic factors has been elusive. Design Casecontrol study aimed at evaluating possible associations between functionally relevant variants of the luteinizing hormone/choriogonadotrophin receptor gene (LHCGR) and PCOS phenotype. Patients A total of 198 PCOS and 187 non-PCOS women, aged 1435 years, of Sardinian origin, were referred to the outpatient clinic of the Department of Obstetrics and Gynaecology of the University of Cagliari (Sardinia). PCOS diagnosis was based on the Rotterdam criteria. Measurements We determined the genotype of ins18LQ, S291N and S312N variants at the LHCGR locus. Genotype was related to the presence or absence of PCOS and to several clinical and biochemical characteristics. Results The presence of at least one 312N allele was strongly associated with PCOS risk (OR, 2.04; 95% CI, 1.323.14; ?2, 10.47; P = 0.001). 312N homozygosity was associated with a further risk increase (OR, 2.73; 95% CI, 1.255.95; ?2, 6.65; P = 0.01). The number of ins18LQ alleles was associated with LH serum levels in controls (?2, 8.04, P = 0.017). Conclusions For the first time, we have identified a genetic variant that is strongly associated with PCOS in an isolated population. These results, if confirmed in other cohorts, may provide the opportunity to test the S312N genotype at the LHCGR locus in fertile women to assess the risk of PCOS. The avoidance of triggering factors like weight increase may improve the reproductive outcome of potentially at-risk subjects.