孕妇磷酸二酯酶8B基因与亚临床甲状腺功能减退的遗传关联研究。

Genetic association study of phosphodiesterase 8B gene with subclinical hypothyroidism in pregnant women.

作者信息

Yang Shuai, Tao Jun, Zhang Junyu, Fan Jianxia, Qian Wei, Shu Khor

机构信息

a Department of Obstetrics and Gynecology and.

b Department of Reproductive Genetics , International Peace Maternity & Child Health Hospital, Shanghai Jiaotong University School of Medicine , Shanghai , P.R. China.

出版信息

Endocr Res. 2015;40(4):199-203. doi: 10.3109/07435800.2015.1015728. Epub 2015 Mar 30.

DOI:10.3109/07435800.2015.1015728

PMID:25822812

Abstract

OBJECTIVE

To explore whether phosphodiesterase 8B (PDE8B) gene is involved in the etiology of subclinical hypothyroidism (SCH) in pregnant women.

METHODS

A total of 180 pregnant patients with SCH and 311 healthy, pregnant control subjects were recruited in this study to detect 4 (rs4704397, rs6885099, rs2046045, and rs12514694 in PDE8B) single nucleotide polymorphisms (SNPs). Univariate associations were studied using Pearson's χ(2) test for categorical variables and Student t/ANOVA tests for continuous ones. Nonparametric Kruskal-Wallis test were used to study the associations of TSH level in different genotypes. Genotyping of SNPs was performed by the MassARRAY(®) iPLEX(®) Gold SNP genotyping analysis technique. The SHEsis program was used to analyze the genotyping data.

RESULTS

There was a significant difference in the rate of high TSH in three genotypes of rs4704397 in all pregnant women. After adjusting for multiple testing by the program SNPSpD, allelic frequencies of rs4704397 (p = 0.016, OR = 1.692), rs6885099 (p = 0.031, OR = 0.621), and rs2046045 (p = 0.023, OR = 0.602) in PDE8B gene showed significant differences between patients with SCH and control subjects. There were no significant differences of genotype frequencies between patients and controls at any of the analyzed SNPs (p > 0.05).The haplotypes ''A G C G'' (p = 0.002; OR, 1.533; 95% CI, 1.172-2.006) and "G A A G" (p = 0.014; OR, 0.576; 95% CI, 0.369-0.899) in PDE8B were observed to be significantly associated with SCH in pregnant women.

CONCLUSION

Genetic variation of the PDE8B gene may be involved in the etiology of SCH in pregnant women.

摘要

目的

探讨磷酸二酯酶8B（PDE8B）基因是否参与孕妇亚临床甲状腺功能减退症（SCH）的病因。

方法

本研究共纳入180例SCH孕妇患者和311例健康孕妇作为对照，检测PDE8B基因的4个单核苷酸多态性（SNP，分别为rs4704397、rs6885099、rs2046045和rs12514694）。分类变量采用Pearson卡方检验，连续变量采用Student t检验或方差分析进行单因素关联研究。采用非参数Kruskal-Wallis检验研究不同基因型与促甲状腺激素（TSH）水平的关联。采用MassARRAY® iPLEX® Gold SNP基因分型分析技术对SNP进行基因分型。使用SHEsis程序分析基因分型数据。

结果

所有孕妇中，rs4704397三种基因型的高TSH发生率存在显著差异。经SNPSpD程序进行多重检验校正后，PDE8B基因的rs4704397（p = 0.016，OR = 1.692）、rs6885099（p = 0.031，OR = 0.621）和rs2046045（p = 0.023，OR = 0.602）的等位基因频率在SCH患者和对照者之间存在显著差异。在任何分析的SNP中，患者和对照者的基因型频率均无显著差异（p > 0.05）。观察到PDE8B基因的单倍型“A G C G”（p = 0.002；OR，1.533；95% CI，1.172 - 2.006）和“G A A G”（p = 0.014；OR，0.576；95% CI，0.369 - 0.899）与孕妇SCH显著相关。