Molecular scanning of the insulin receptor gene in women with polycystic ovarian syndrome.
Molecular scanning of the insulin receptor gene in women with polycystic ovarian syndrome.
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多囊卵巢综合征女性胰岛素受体基因的分子扫描。
DOI：
10.1210/jcem.81.5.8626868
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
R. Clayton
中科院分区：
文献类型：
--
作者：
J. Talbot;E. J. Bicknell;M. Rajkhowa;A. Krook;S. O’Rahilly;R. Clayton
多囊卵巢综合征（PCOS）是一种常见的以慢性无排卵、不孕、高雄激素血症和胰岛素抵抗为特征的疾病。本研究调查了胰岛素受体基因突变是否可以解释PCOS患者的胰岛素抵抗。从总共108名PCOS妇女中，选择了一个24人的亚组，其标准是通过空腹血清胰岛素、75 g口服葡萄糖耐量试验后的胰岛素曲线下面积和内源性葡萄糖处置作为胰岛素敏感性的测量来评估胰岛素抵抗的上四分位数。另外还调查了5名正常妇女。使用基因组DNA通过PCR扩增胰岛素受体基因的整个编码区，包括22个外显子，然后进行单链构象多态性（SSCP）分析以筛选单碱基DNA序列变化。DNA测序显示，SSCP变异体在外显子3、6-8、11、13、15、17和22的区域中检测到。外显子3、6、7、11、15和22区域的SSCP变异是由外显子侧翼内含子区域内的核苷酸取代引起的。在外显子3的5'内含子中观察到的相当大的变异被发现是由（ATTT，8-11）和（TC，10-13）短序列重复的数目的变异引起的。外显子8（Asp 519，Ala 523），13（Asn 838）和17（Tyr 984，His 1058）的SSCP变异由已知的沉默多态性引起。Southern印迹实验排除了主要基因缺失、插入或重排。我们的结论是，PCOS患者的胰岛素抵抗通常不是胰岛素受体基因的错义或无义突变的结果。
Polycystic ovary syndrome (PCOS) is a common disorder characterized by chronic anovulation and infertility, hyperandrogenaemia, and frequently insulin resistance. This study investigated whether mutations in the insulin receptor gene could explain the insulin resistance in subjects with PCOS. From a total of 108 women with PCOS, a subgroup of 24 were selected on the criteria of being in the upper quartile for insulin resistance as assessed by fasting serum insulin, insulin area under the curve following 75 g oral glucose tolerance test, and endogenous glucose disposal as a measure of insulin sensitivity. An additional five normal women were also investigated. The entire coding region of the insulin receptor gene, comprising of 22 exons, was amplified by the PCR using genomic DNA and then subjected to single-stranded conformation polymorphism (SSCP) analysis to screen for single-base DNA sequence changes. DNA sequencing revealed that SSCP variants were detected in regions encompassing exons 3, 6-8, 11, 13, 15, 17, and 22. SSCP variants in regions of exons 3, 6, 7, 11, 15 and 22 were caused by nucleotide substitutions within intronic regions flanking the exon. The considerable variation seen in the 5' intron of exon 3 was found to be caused by variation in the number of (ATTT, 8-11) and (TC, 10-13) short sequence repeats. SSCP variants in exons 8 (Asp519, Ala523), 13 (Asn 838), and 17 (Tyr984, His1058) were caused by known silent polymorphisms. Southern blotting experiments excluded major gene deletions, insertions, or rearrangements. We conclude that insulin resistance in subjects with PCOS is not commonly a consequence of missense or nonsense mutations in the insulin receptor gene.
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DOI：
10.1210/jcem.75.2.1322430
发表时间：
1992-08
期刊：
The Journal of clinical endocrinology and metabolism
影响因子：
--
作者：
T. Ciaraldi;A. El-Roeiy;Z. Madar;D. Reichart;J. Olefsky;S. Yen
通讯作者：
T. Ciaraldi;A. El-Roeiy;Z. Madar;D. Reichart;J. Olefsky;S. Yen
墨西哥裔美国人胰岛素受体基因座外显子 3 附近并置的短序列重复类型和单倍型。
影响因子：
4.4
作者：
Hanis,CL;Bertin,TK
通讯作者：
Bertin,TK
影响因子：
4.4
作者：
SHEFFIELD, VC;BECK, JS;STONE, EM
通讯作者：
STONE, EM
影响因子：
158.5
作者：
MOLLER, DE;FLIER, JS
通讯作者：
FLIER, JS
正常人卵巢中胰岛素和胰岛素样生长因子 I 受体的分布和特征。
DOI：
10.1210/jcem-61-4-728
发表时间：
1985
期刊：
The Journal of clinical endocrinology and metabolism
影响因子：
--
作者：
Poretsky,L;Grigorescu,F;Seibel,M;Moses,AC;Flier,JS
通讯作者：
Flier,JS