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

Shuai Yang, Jun Tao, Junyu Zhang, Jianxia Fan, Wei Qian, Khor Shu
Author Information
  1. Shuai Yang: a Department of Obstetrics and Gynecology and.
  2. Jun Tao: a Department of Obstetrics and Gynecology and.
  3. Junyu Zhang: b Department of Reproductive Genetics , International Peace Maternity & Child Health Hospital, Shanghai Jiaotong University School of Medicine , Shanghai , P.R. China.
  4. Jianxia Fan: a Department of Obstetrics and Gynecology and.
  5. Wei Qian: a Department of Obstetrics and Gynecology and.
  6. Khor Shu: a Department of Obstetrics and Gynecology and.

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.

Keywords

MeSH Term

3',5'-Cyclic-AMP Phosphodiesterases
Adult
Female
Genetic Association Studies
Genotype
Humans
Hypothyroidism
Polymorphism, Single Nucleotide
Pregnancy
Pregnancy Complications

Chemicals

3',5'-Cyclic-AMP Phosphodiesterases
PDE8B protein, human

Word Cloud

Created with Highcharts 10.0.0pregnantPDE8BgeneSCHwomenp = 08Bsubclinicalhypothyroidismpatientsstudyrs4704397SNPssignificantphosphodiesteraseinvolvedetiologycontrolsubjectsrs6885099rs2046045singlenucleotideassociationstestusedTSHgenotypes®genotypingprogramfrequenciesOR = 0differencesOR195%CI0GeneticOBJECTIVE:explorewhetherMETHODS:total180311healthyrecruiteddetect4rs12514694polymorphismsUnivariatestudiedusingPearson'sχ2categoricalvariablesStudentt/ANOVAtestscontinuousonesNonparametricKruskal-WallisleveldifferentGenotypingperformedMassARRAYiPLEXGoldSNPanalysistechniqueSHEsisanalyzedataRESULTS:differenceratehighthreeadjustingmultipletestingSNPSpDallelic016OR = 1692031621023602showedgenotypecontrolsanalyzedp > 005Thehaplotypes''AGCG''002533172-2006"GG"014576369-0899observedsignificantlyassociatedCONCLUSION:variationmayassociationPhosphodiesterasepregnancypolymorphism

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