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钙蛋白酶-10单倍型组合及其与妊娠期糖尿病的关联。

Calpain-10 haplotype combination and association with gestational diabetes mellitus.

作者信息

Leipold Heinz, Knöfler Martin, Gruber Christian, Haslinger Peter, Bancher-Todesca Dagmar, Worda Christof

机构信息

Department of Obstetrics and Gynaecology, University of Vienna Medical School, Waehringer Guertel 18-20, Vienna, Austria.

出版信息

Obstet Gynecol. 2004 Jun;103(6):1235-40. doi: 10.1097/01.AOG.0000127790.15556.3d.

Abstract

OBJECTIVE

Gestational diabetes mellitus (GDM) is a frequent complication of pregnancy. Epidemiologic and pathophysiologic data suggest a close link of this disease to non-insulin-dependent diabetes mellitus. Within the calpain-10 gene various single-nucleotide polymorphisms have been identified that increased the risk for non-insulin-dependent diabetes mellitus. Therefore, we examined single-nucleotide exchanges of this gene in women with GDM.

METHODS

A total of 875 unselected women were prospectively screened for GDM. Eighty women of this population, 40 patients with an abnormal oral glucose tolerance test and 40 normal controls, were randomly selected. DNA samples isolated from sera of the control and study groups were analyzed with respect to single-nucleotide polymorphisms of the calpain-10 gene at positions 43, 19, and 63 using polymerase chain reaction amplification and restriction analysis.

RESULTS

Women with GDM were more likely to be homozygous for the allele 1 of single-nucleotide polymorphism 63 (P =.02 by chi(2) test). With respect to single-nucleotide polymorphisms 19 and 43, no significant differences in allele distribution were detected between controls and women with GDM. When comparing the different haplotypes for calpain-10 (single-nucleotide polymorphisms 43, 19, and 63), all women with the haplotype combination 121/221 (n = 8) had gestational diabetes (P =.005 by Fisher exact test).

CONCLUSION

Our results indicate that the haplotype 121/221 of the calpain-10 gene may be associated with disturbances of glucose metabolism during pregnancy.

LEVEL OF EVIDENCE

II-1

摘要

目的

妊娠期糖尿病(GDM)是孕期常见的并发症。流行病学和病理生理学数据表明,该疾病与非胰岛素依赖型糖尿病密切相关。在钙蛋白酶-10基因中已鉴定出多种单核苷酸多态性,这些多态性增加了患非胰岛素依赖型糖尿病的风险。因此,我们检测了GDM女性中该基因的单核苷酸交换情况。

方法

对总共875名未经筛选的女性进行GDM的前瞻性筛查。从该人群中随机选取80名女性,其中40名口服葡萄糖耐量试验异常的患者和40名正常对照。使用聚合酶链反应扩增和限制性分析,对从对照组和研究组血清中分离的DNA样本进行钙蛋白酶-10基因第43、19和63位单核苷酸多态性分析。

结果

GDM女性更有可能是单核苷酸多态性63的等位基因1的纯合子(χ²检验,P = 0.02)。关于单核苷酸多态性19和43,对照组与GDM女性之间未检测到等位基因分布的显著差异。比较钙蛋白酶-10的不同单倍型(单核苷酸多态性43、19和63)时,所有单倍型组合为121/221的女性(n = 8)均患有妊娠期糖尿病(Fisher精确检验,P = 0.005)。

结论

我们的结果表明,钙蛋白酶-10基因的单倍型121/221可能与孕期糖代谢紊乱有关。

证据级别

II-1

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