Human Molecular Genetics Research Group, Department of Biotechnology, Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
Fertil Steril. 2013 Jun;99(7):1930-6.e6. doi: 10.1016/j.fertnstert.2013.02.019. Epub 2013 Mar 15.
To confirm the effect of single nucleotide polymorphisms (SNPs) in chorionic gonadotropin beta (CGB) genes in modulating the susceptibility to recurrent miscarriage (RM) in Danes and in a meta-analysis across Danes and the discovery samples from Estonia and Finland.
Case-control association study, restriction fragment length polymorphism genotyping, resequencing.
Fertility clinics at the Rigshospitalet, Copenhagen, and Aalborg Hospital, Aalborg, Denmark.
PATIENT(S): Four hundred fifty Danish women and men from couples with RM and 119 women with children and no miscarriages in new study. A total of 634 women and men from RM couples and 314 female controls in a combined study of Estonians, Finns, and Danes.
INTERVENTION(S): None.
MAIN OUTCOME MEASURE(S): Distribution of CGB5 and CGB8 allele and haplotype frequencies in patients and controls.
RESULT(S): For the majority of studied SNPs, the allelic and haplotypic distribution differed statistically between the Danish and the previous Estonian-Finnish sample. In Danes, two CGB5 promoter SNPs (c5-155; c5-142) exhibited a nonsignificant trend for higher allele frequency in fertile women compared with RM patients. The meta-analysis of results from three populations confirmed a modest but significant effect on carriage of c5-155C (odds ratio = 0.64; 95% confidence interval [CI] 0.44-0.94) and c5-142A (odds ratio = 0.66; 95% CI, 0.45-0.94) variants in reducing the risk of RM. None of the investigated genetic variants in the CGB8 gene was associated with RM.
CONCLUSION(S): Carriage of particular variants in the promoter of the CGB5 gene seems to protect against RM. No common genetic variants in CGB5 and CGB8 were associated with increased RM susceptibility in the studied North European populations.
确认在丹麦人群中，以及在对丹麦、爱沙尼亚和芬兰发现样本进行的荟萃分析中，绒毛膜促性腺激素β（CGB）基因中单核苷酸多态性（SNPs）对复发性流产（RM）易感性的调节作用。
病例对照关联研究、限制性片段长度多态性基因分型、重测序。
丹麦哥本哈根的里格医院和奥尔堡的奥尔堡医院的生育诊所。
450 名来自 RM 夫妇的丹麦男女患者和 119 名新研究中生育孩子且无流产的女性。总共 634 名 RM 夫妇的男女患者和 314 名爱沙尼亚、芬兰和丹麦联合研究的女性对照。
无。
患者和对照组中 CGB5 和 CGB8 等位基因和单倍型频率的分布。
对于大多数研究的 SNP，丹麦人和之前的爱沙尼亚-芬兰样本之间在等位基因和单倍型分布上存在统计学差异。在丹麦人中，两个 CGB5 启动子 SNP（c5-155；c5-142）在携带 c5-155C 的可育女性中显示出与 RM 患者相比，等位基因频率升高的非显著趋势。三个人群的结果荟萃分析证实，c5-155C（比值比=0.64；95%置信区间[CI]0.44-0.94）和 c5-142A（比值比=0.66；95%CI，0.45-0.94）变异的携带可降低 RM 的风险，这是适度但显著的效应。在 CGB8 基因中没有研究的遗传变异与 RM 相关。
CGB5 基因启动子中特定变异的携带似乎可以预防 RM。在研究的北欧人群中，CGB5 和 CGB8 中没有常见的遗传变异与 RM 易感性增加相关。
