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Phosphodiesterase 8B gene polymorphism in women with recurrent miscarriage: A retrospective case control study.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi. (Obstetrisk forskning/Högberg)
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi. (Klinisk och experimentell reproduktionsbiologi/Olovsson)
Department of Clinical Sciences, Division of Obstetrics and Gynaecology, Karolinska Institutet and Danderyd Hospital, Stockholm, Sweden.
Department of Clinical Sciences, Division of Obstetrics and Gynaecology, Karolinska Institutet and Danderyd Hospital, Stockholm, Sweden.
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2012 (engelsk)Inngår i: BMC Medical Genetics, ISSN 1471-2350, E-ISSN 1471-2350, Vol. 13, s. 121-Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

sted, utgiver, år, opplag, sider
2012. Vol. 13, s. 121-
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Identifikatorer
URN: urn:nbn:se:uu:diva-188671DOI: 10.1186/1471-2350-13-121ISI: 000314113200001PubMedID: 23237535OAI: oai:DiVA.org:uu-188671DiVA, id: diva2:578633
Tilgjengelig fra: 2012-12-18 Laget: 2012-12-18 Sist oppdatert: 2017-12-06bibliografisk kontrollert
Inngår i avhandling
1. Hypothyroidism and Pregnancy
Åpne denne publikasjonen i ny fane eller vindu >>Hypothyroidism and Pregnancy
2015 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
Abstract [en]

Hypothyroidism is a common endocrine disorder affecting women of reproductive age. On a global level, iodine deficiency is still the most common cause of hypothyroidism. Also genetic variations, in particular SNP rs4704397 in the PDE8B gene, are responsible for a significant proportion of TSH variations.  Untreated hypothyroidism has significant adverse effects on pregnancy and fetal outcome. Most international guidelines suggest targeted thyroid testing in pregnant women with risk factors for thyroid disturbances.

In a case-control study, an association between homozygous A/A as well as homozygous G/G carriers of SNP rs 4704397 in PDE8B and recurrent miscarriage was found. The explanation for this association is unknown.

In a nationwide survey, all guidelines for thyroid testing and management of hypothyroidism during pregnancy in Sweden were collected and compared with international guidelines. The local guidelines were variable and poorly compliant with the international guidelines.

In a follow-up in one district, 5,254 pregnant women were included for subsequent review of their medical reports. We found a targeted thyroid testing rate of 20.1% in clinical practice, with an overall frequency of women with trimester-specific elevated TSH of 18.5%. More disturbingly, half of the women who were on levothyroxine treatment at the time of conception had an elevated TSH level at thyroid testing.

In a subsequent cohort study of the 5,254 women, we found the prevalence of trimester-specific elevated TSH and overt hypothyroidism to be equal in targeted thyroid tested and untested women.

In a cross-sectional study, a median urinary iodine concentration (UIC) of 98 μg/l was found in the study population. According to WHO/UNICEF/IGN criteria, the population-based median UIC during pregnancy should be 150-249 μg/l.

In conclusion, genetic variations may contribute to adverse pregnancy outcomes. In clinical practice, thyroid testing and the management of hypothyroidism during pregnancy is unsatisfactory, regarding the whole chain from development of local guidelines to their implementation and to targeted thyroid testing. Moreover, our results indicate insufficient iodine status in the pregnant population of Sweden.

sted, utgiver, år, opplag, sider
Uppsala: Acta Universitatis Upsaliensis, 2015. s. 69
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1081
Emneord
phosphodiesterase 8B, recurrent miscarriage, single nucleotide polymorphism, thyroid, guidelines, hypothyroidism, pregnancy, survey, thyroid testing, screening, iodine, iodine deficiency, median urinary iodine concentration
HSV kategori
Forskningsprogram
Obstetrik och gynekologi
Identifikatorer
urn:nbn:se:uu:diva-247090 (URN)978-91-554-9201-4 (ISBN)
Disputas
2015-05-08, Rosénsalen, Akademiska sjukhuset, ingång 95/96. Barn- och kvinnosjukhuset. NBV (nedre bottenvåning)., Uppsala, 09:00 (svensk)
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Veileder
Tilgjengelig fra: 2015-04-17 Laget: 2015-03-13 Sist oppdatert: 2015-07-07

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