Phosphodiesterase 8B gene polymorphism in women with recurrent miscarriage: A retrospective case control study

Michaela Granfors,Katarina Bremme,Helena Karypidis,Inger Sundström-Poromaa,Anneli Stavreus-Evers,Helena Åkerud,Britth-Marie Landgren,Anna-Karin Wikström,Frida Hosseini,Lottie Skjöldebrand-Sparre

doi:10.1186/1471-2350-13-121

Abstract

BackgroundRecurrent miscarriage affects approximately 1% of all couples. There is a known relation between hypothyroidism and recurrent miscarriage. Phosphodiesterase 8B (PDE8B) is a regulator of cyclic adenosine monophosphate (cAMP) with important influence on human thyroid metabolism. Single nucleotide polymorphism (SNP) rs 4704397 in the PDE8B gene has been shown to be associated with variations in serum Thyroid Stimulating Hormone (TSH) and thyroxine (T4) levels. The aim of this study was to investigate whether there is an association between the SNP rs 4704397 in the PDE8B gene and recurrent miscarriage.MethodsThe study was designed as a retrospective case control study. 188 cases with recurrent miscarriage were included and compared with 391 controls who had delivered at least once and with no history of miscarriage or assisted reproduction.ResultsNo difference between cases and controls concerning age was found. Bivariate associations between homozygous A/A (OR 1.57, 95% CI 0.98-2.52) as well as G/G carriers (OR 1.52, 95% CI 1.02-2.25) of SNP rs 4704397 in PDE8B and recurrent miscarriage were verified (test for trend across all 3 genotypes, p = 0.059). After adjustment for known confounders such as age, BMI and smoking the association between homozygous A/A (AOR 1.63, 95% CI 1.01 - 2.64, p = 0.045) and G/G (AOR 1.52, 95% CI 1.02 - 2.27, p = 0.039) carriers of SNP rs 4704397 in PDE8B and recurrent miscarriage remained.ConclusionsOur findings suggest that there is an association between homozygous A/A as well as homozygous G/G carriers of SNP rs 4704397 in PDE8B and recurrent miscarriage.

Highlights

Recurrent miscarriage affects approximately 1% of all couples
Based on a recent genome-wide association study, six different single nucleotide polymorphisms (SNP) in the Phosphodiesterase 8B (PDE8B) gene were associated with increased serum concentrations of thyroid stimulating hormone (TSH) [14]
Values are mean ± standard deviation; n, numbers of women; BMI, body mass index: BMI at inclusion, BMI at first antenatal visit; Smokers: smoker during ≥1 pregnancy ending with miscarriage, smoker at first visit to the prenatal center in gestational week 10; Hypothyroidism: elevated serum Thyroid Stimulating Hormone (TSH)-levels according to local laboratory limits

Summary

Introduction

Recurrent miscarriage affects approximately 1% of all couples. Single nucleotide polymorphism (SNP) rs 4704397 in the PDE8B gene has been shown to be associated with variations in serum Thyroid Stimulating Hormone (TSH) and thyroxine (T4) levels. The aim of this study was to investigate whether there is an association between the SNP rs 4704397 in the PDE8B gene and recurrent miscarriage. The human phosphodiesterase type 8B (PDE8B) gene is located at human chromosome 5q14.1 in intron 1 and encodes a high affinity cyclic adenosine monophosphate (cAMP) specific nucleotide phosphodiesterase [9,10,11]. Based on a recent genome-wide association study, six different single nucleotide polymorphisms (SNP) in the PDE8B gene were associated with increased serum concentrations of thyroid stimulating hormone (TSH) [14]. The association between SNP rs 4704397 in PDE8B and levels of TSH has been confirmed in pregnant women, no association with free T3 or T4 levels was found [17]

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