PP009. A follow-up study of Finnish pre-eclampsia families identifies a new fetal susceptibility locus on chromosome 18

H M Laivuori; K K Majander; P Villa; K Kivinen; J Kere

doi:10.1016/j.preghy.2012.04.120

PP009. A follow-up study of Finnish pre-eclampsia families identifies a new fetal susceptibility locus on chromosome 18

Pregnancy Hypertens. 2012 Jul;2(3):244-5. doi: 10.1016/j.preghy.2012.04.120. Epub 2012 Jun 13.

Authors

H M Laivuori¹, K K Majander¹, P Villa², K Kivinen³, J Kere⁴

Affiliations

¹ Haartman Institute, Medical Genetics, Finland; Research Programs Unit, Women's Health, University of Helsinki, Finland.
² Department of Obstetrics and Gynaecology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
³ Wellcome Trust Genome Campus, Hinxton, Wellcome Trust Sanger Institute, Cambridge, United Kingdom.
⁴ Haartman Institute, Medical Genetics, Finland; Department of Biosciences and Nutrition, and Science for Life Laboratory, Karolinska Institute, Stockholm, Sweden; Folkhälsan Institute of Genetics, Helsinki, Finland.

PMID: 26105332
DOI: 10.1016/j.preghy.2012.04.120

Abstract

Introduction: According to the epidemiological research both maternal and fetal genes influence in predisposition to pre-eclampsia (PE). We have previously detected linkage signals in Finnish families on chromosomes 2p25, 4q32, and 9p13 using maternal phenotypes.

Objectives: Our aim was to perform a follow-up linkage analysis using updated maternal phenotypes and an unprecedented linkage analysis using fetal phenotypes.

Methods: We performed a non-parametric linkage analysis using the same sample set and microsatellite markers as reported in the original linkage study (Laivuori et al., [1]). Markers genotyped were available from 237 individuals in 15 Finnish families including 72 affected mothers (pregnancy complicated by PE n=54, eclampsia n=1, or gestational hypertension [GHT] n=17), and 49 affected fetuses (born from a pregnancy complicated by PE n=45, or GHT n=4). MERLIN software (Abecasis et al., 2002) was used for sample and marker quality control and linkage analysis. Results from this study were compared against the original results obtained by using GENEHUNTER 2.1 software.

Results: The maximum nonparametric linkage (NPL) scores on chromosome 2 were at 21.70cM near marker D2S168 using maternal and fetal phenotypes (NPL score 3.79, p=0.00008, and NPL score 2.95, p=0.002, respectively). On chromosome 4 the highest peak was at 158.20 cM near marker D4S413 using maternal phenotypes (NPL score 3.13 p=0.0009), and at 109.60 cM near marker D4S1572 using fetal phenotypes (NPL score 2.50, p=0.006). On chromosome 9 the highest peaks using maternal phenotypes were at 38.90cM near marker D9S169 (NPL=3.76, p=0.00008), and at 120.80 cM near marker D9S1811 (NPL=2.74, p=0.003). The maximum peak on chromosome 9 using fetal phenotypes was found at 59.20cM near marker D9S175 (NPL=2.69, p=0.004). We found a suggestive linkage on chromosome 18 at 86.80cM near marker D18S64 using fetal phenotypes (NPL score of 2.51, p=0.006), but the highest peak using maternal phenotypes did not reach significance.

Conclusion: In this follow-up study we have confirmed the linkage signals identified in the original linkage analysis using maternal phenotypes. Linkage to chromosome 2 was also supported by analysis using fetal phenotypes. Chromosome 18 may harbour a new fetal susceptibility locus for PE.