Genetic evidence of multiple loci in dystocia--difficult labour.
BACKGROUND
Dystocia, difficult labour, is a common but also complex problem during childbirth. It can be attributed to either weak contractions of the uterus, a large infant, reduced capacity of the pelvis or combinations of these. Previous studies have indicated that there is a genetic component in the susceptibility of experiencing dystocia. The purpose of this study was to identify susceptibility genes in dystocia.


METHODS
A total of 104 women in 47 families were included where at least two sisters had undergone caesarean section at a gestational length of 286 days or more at their first delivery. Study of medical records and a telephone interview was performed to identify subjects with dystocia. Whole-genome scanning using Affymetrix genotyping-arrays and non-parametric linkage (NPL) analysis was made in 39 women exhibiting the phenotype of dystocia from 19 families. In 68 women re-sequencing was performed of candidate genes showing suggestive linkage: oxytocin (OXT) on chromosome 20 and oxytocin-receptor (OXTR) on chromosome 3.


RESULTS
We found a trend towards linkage with suggestive NPL-score (3.15) on chromosome 12p12. Suggestive linkage peaks were observed on chromosomes 3, 4, 6, 10, 20. Re-sequencing of OXT and OXTR did not reveal any causal variants.


CONCLUSIONS
Dystocia is likely to have a genetic component with variations in multiple genes affecting the patient outcome. We found 6 loci that could be re-evaluated in larger patient cohorts.
Algovik
Michael
M
Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden. michael.algovik@ltkalmar.se
Kivinen
Katja
K
Peterson
Hanna
H
Westgren
Magnus
M
Kere
Juha
J
D000328:Adult; D004420:Dystocia / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D056426:Genetic Loci / Q000235:genetics*; D006801:Humans; D007407:Interviews as Topic; D007743:Labor, Obstetric / Q000235:genetics*; D010121:Oxytocin / Q000235:genetics; D011247:Pregnancy; D018045:Receptors, Oxytocin / Q000235:genetics; D012015:Reference Standards; D017422:Sequence Analysis, DNA; D035781:Siblings; D055815:Young Adult
D018045:Receptors, Oxytocin; D010121:Oxytocin