Open Access Research article

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

Michaela Granfors1*, Helena Karypidis12, Frida Hosseini2, Lottie Skjöldebrand-Sparre2, Anneli Stavreus-Evers1, Katarina Bremme3, Britth-Marie Landgren4, Inger Sundström-Poromaa1, Anna-Karin Wikström1 and Helena Åkerud1

Author Affiliations

1 Department of Women’s and Children’s Health, Uppsala University, Uppsala, Sweden

2 Department of Clinical Sciences, Division of Obstetrics and Gynaecology, Karolinska Institutet and Danderyd Hospital, Stockholm, Sweden

3 Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden

4 Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden

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BMC Medical Genetics 2012, 13:121  doi:10.1186/1471-2350-13-121

Published: 13 December 2012



Recurrent 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.


The 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.


No 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.


Our 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.

Phosphodiesterase 8B; Recurrent miscarriage; Single nucleotide polymorphism; Thyroid