当女性的卵巢囊肿阻断正常排卵和月经周期时，就会发生多囊卵巢综合征（Polycystic ovary syndrome， PCOS）。这个问题表面上很简单，但事实上，这种疾病是很复杂的，涉及到多遗传组分和环境因素。受PCOS影响的女性占到女性总人口的5%，而且那些被诊断为PCOS的女性发展为2型糖尿病（T2DM）的危险性是其他人的2到7倍。正是由于这个原因，研究人员相信一个糖尿病相关基因也许在PCOS的发生当中起作用。一项由146名PCOS患者组成的最新研究表明“糖尿病基因”calpain-10（CAPN10）实际上是能够解释该综合症的一个令人感兴趣的候选基因。
一项新研究
一项题名为“白种人群中钙蛋白酶-10的变异体和单倍体与多囊卵巢综合症相关”的新研究包含了这些研究结果。该研究由位于德国Neuherberg的GSF-国家环境和健康研究中心的Caren Vollmert, Claudia Lamina, Cornelia Huth, Melanie Kolz, Andreas Schopfer-Wendels, Friedhelm Bongardt, Florian Kronenberg, Hannelore Lowel 和 Thomas Illig；位于Essen的Duisburg-Essen大学的Susanne Hahn,Klaus Mann and Onno E. Janssen；Munich的Ludwig Maximilians大学的H.-Erich Wichmann；Munich 技术大学的Jakob C. Mueller；Dusseldorf的Heinrich Heine大学的Christian Herder以及GSF-国家环境和健康研究中心的Rolf Holle共同完成。
他们的研究发表在美国内分泌代谢生理学杂志的网络版（http://ajpendo.physiology.org/）。该杂志是美国生理学会（APS）（http://www.the-aps.org/）每月发行的14种科学出版物之一。
方法
研究包括752名女性。其中，146人诊断为PCOS，其余606人用来作为对照的德国人来自先前进行的与本研究无关的一项研究，且为无关的非糖尿病女性。
PCOS组分离外周血并提取基因组DNA，对照组从全血粒细胞中提取基因组DNA。鉴定出8 个CAPN10变异体的基因型：UCSNP-44，-43，-56，ins/del-19（CAPN10 基因UCSNP-19位点的片段，包含DNA序列中的插入或缺失变异），-110， -58， -63，和 -22。
研究人员提取了这8个特殊的单核苷酸多肽性片断（SNPs）iV--发生在人类DNA序列的一种微小的遗传变异，因为它们和PCOS，2型糖尿病或相关症状有关。然后用比较DNA分析的方法做基因分型来判定个体对某种疾病的遗传缺陷。
为估计每个SNPs与PCOS的遗传关系，研究人员测定了病例组和对照组基因型分布的差异。还计算了两组中年龄和体重指数（BMI）的不同产生的影响。研究人员用他们自己获得的数据以及所有的已经发表的能表明CAPN10和PCOS的遗传关系的数据做了meta-分析，来更好的阐明CAPN10和PCOS的遗传关系。
结果
研究人员的发现包括以下要点：
* 有明显的证据表明糖尿病的基因区域CAPN10 UCSNP-56 和 UCSNP-ins/del-19与PCOS易感性有关系。
* CAPN10 UCSNP-22和PCOS之间有预期关系。
* CAPN10 UCSNP-44， -43， -110， -58，or -63和PCOS易感性没有显著关系。
结论
本研究进一步为一个基因的两个区域CAPN10 UCSNP-56 和 UCSNP-ins/del-19与PCOS易感性相关的理论提供了强有力的支持。这些数据也表明SNP ins/del-19可能与PCOS和2型糖尿病都有关系。
这些结果对于约占女性人口5%，被诊断患有这种疼痛甚至致残的疾病的患者而言是个福音。同时，作者们建议进行进一步的病例-对照研究和meta-分析来更好的解释这些结果。
'Diabetes Gene' And Polycystic Ovary Syndrome May Be Linked
Main Category: Diabetes News
Article Date: 11 Dec 2006 - 20:00pm (PST)
Polycystic ovary syndrome (PCOS) occurs when ovarian cysts block a woman's normal ovulation and menstrual cycle. While the problem sounds straightforward, the disease is complex, born from both multiple genetic components and environmental factors. PCOS affects up to five percent of the female population, and those diagnosed with the disease have a 2- to 7-fold risk of developing type 2 diabetes mellitus (T2DM). For this reason researchers believe a gene related to diabetes may also play a role in the onset of PCOS. A new study of 146 PCOS patients has found that the "diabetes gene" (calpain-10 (CAPN10)) is in fact an interesting candidate for explaining the syndrome.
A New Study
The findings are contained in a new study entitled "Calpain-10 Variants and Haplotypes are Associated with Polycystic Ovary Syndrome in Caucasians." The study was conducted by Caren Vollmert, Claudia Lamina, Cornelia Huth, Melanie Kolz, Andreas Schopfer-Wendels, Friedhelm Bongardt, Florian Kronenberg, Hannelore Lowel and Thomas Illig, all of the GSF-National Research Center for Environment and Health, Neuherberg; Susanne Hahn, Klaus Mann and Onno E. Janssen, University of Duisburg-Essen, Essen; H.-Erich Wichmann, Ludwig Maximilians University, Munich; Jakob C. Mueller, Technical University, Munich; Christian Herder, Heinrich Heine University, Dusseldorf; and Rolf Holle, GSF-National Research Center of Environment and Health, Neuherberg, Germany.
Their study appears in the online edition of the American Journal of Physiology-Endocrinology and Metabolism (http://ajpendo.physiology.org/). The journal is one of the 14 scientific publications published by the American Physiological Society (APS) (http://www.the-aps.org/) each month.
Methodology
The study comprised 752 females. Of the total, 146 were diagnosed with PCOS and 606 were unrelated non-diabetic female controls drawn from a previously conducted independent study of the German population.
Genomic DNA was taken from the PCOS group and isolated from whole blood, and genomic DNA was extracted from the blood leukocytes of the controls. Eight CAPN10 variants were genotyped: UCSNP-44, -43, -56, ins/del-19 (a fragment of gene CAPN10 UCSNP-19, which contains an insertion or deletion variation in the DNA sequence), -110, -58, -63, and -22.
The researchers extracted these eight specific single-nucleotide polymorphisms (SNPs) ¡V the small genetic variations that can occur within a person's DNA sequence because they are known to be associated with PCOS, type 2 diabetes, or related traits. Genotyping using comparative DNA analysis to determine the predisposition of individuals to certain diseases was then performed.
To estimate the genetic association of each of the eight SNPs with PCOS the differences in genotype distributions between the case and control groups were measured. The impact of the differences in age and body mass index (BMI) structures for both groups was also calculated. To better clarify the purported associations between CAPN10 and PCOS the researchers performed a meta-analysis using their own data and all available published data showing a genetic association between CAPN10 and PCOS.
Results
Highlights of the researchers' findings include the following:
* clear evidence associating the diabetes gene areas CAPN10 UCSNP-56 and UCSNP-ins/del-19 with PCOS susceptibility
* an expected association between CAPN10 UCSNP-22 and PCOS
* no significant association between CAPN10 UCSNP-44, -43, -110, -58, or -63 and PCOS susceptibility
Conclusions
This study provides additional strong support for the theory that two areas of one gene -- CAPN10 UCSNP-56 and UCSNP-ins/del-19 -- are related to PCOS susceptibility. These data also suggest that the SNP ins/del-19 may be related to both PCOS and type 2 diabetes.
The findings are good news for the estimated five percent of the female population who are diagnosed with the painful and sometimes disabling disease. At the same time, the authors recommend that additional case-control studies and meta-analysis be undertaken to better understand these findings.
http://www.medicalnewstoday.com/medicalnews.php?newsid=58401
编辑：蓝色幻想
