189800 PREECLAMPSIA/ECLAMPSIA 1; PEE1
Alternative
titles; symbols
PEE
TOXEMIA OF PREGNANCY
table OF
CONTENTS
Gene Map Locus: 7q36,
4q25-q34
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TEXT
Preeclampsia is otherwise known as gestational
proteinuric hypertension (Davey
and MacGillivray, 1988). So defined,
preeclampsia probably identifies a rather
homogeneous disease entity. A high proportion of
patients so defined have glomerular endotheliosis,
the unique histopathologic feature of the condition
(Fisher et al., 1981).
Although proper obstetric care has made eclampsia a
relatively rare event in the Western world,
preeclampsia occurs in 2 to 4% of all pregnancies
in the United States and the United Kingdom. Most
cases occur in first pregnancies.
Humphries (1960)
presented a systematic study of hypertensive
toxemia of pregnancy in mother-daughter pairs
delivered at The Johns Hopkins Hospital. Toxemia
occurred in 28% of daughters of women who had
toxemia in the pregnancy in which they were
delivered as compared with 13% in a comparison
group. Chesley et al.
(1968) did a similar study with similar
results. In cases in which 2 or more daughters of
an eclamptic woman have been tested in pregnancy,
toxemia developed in the first pregnancy of at
least 1 daughter in 53% of the families. No
definite conclusions on genetic heterogeneity, role
of maternal versus fetal genotype, and possible
genotype-genotype interaction were reached by
Cooper and Liston (1979).
Editorials published in The Lancet (Anonymous,
1980, 1988)
and in the British Medical Journal (Anonymous,
1980) gave excellent reviews of genetic studies
on eclampsia. Cooper et al.
(1988) reported several examples of 3- and
4-generation involvement. Despite this, pedigree
analysis by Chesley and
Cooper (1986) suggested autosomal recessive
inheritance with a frequency of the 'abnormal'
allele of approximately 0.25. Arngrimsson
et al. (1990) did a study through 3 or 4
generations in 94 families in Iceland patterned
after the Humphries
(1960) study. The families were descended from
index women who were delivered in the years 1931-47
and who had either eclampsia or severe
preeclampsia. Inheritance was followed through both
sons and daughters. They concluded that either a
recessive or a dominant model could fit the data.
Kilpatrick et al. (1989)
studied a group of 56 women who had had proteinuric
preeclampsia and who had parous sisters. In the
first pregnancy, proteinuric preeclampsia was more
common in the sisters than in the maternity
hospital population; the relative risk was 6.0.
Frequency of HLA-DR4 was higher in sisters with
pregnancy-induced hypertension than in sisters with
normotensive pregnancies and more of them shared
HLA-DR4 with their spouses. Kilpatrick
et al. (1989) referred to a study of unrelated
women in which they confirmed the association
between DR4 and proteinuric preeclampsia. They
proposed the hypothesis that preeclampsia occurs
when both mother and fetus are homozygous for an
HLA-linked recessive gene. Wilton
et al. (1990), however, excluded close linkage
of an eclampsia susceptibility gene with HLA.
Liston and Kilpatrick
(1991) examined 6 simple mendelian models of
inheritance and rejected all except the one in
which both mother and fetus must express the same
recessive gene to confer susceptibility. They
considered this model to be consistent with the
putative association with HLA-DR4.
Based on the hypothesis that preeclampsia occurs
in women who are homozygous for a relatively common
susceptibility gene, Hayward
et al. (1992) constructed an exclusion map by
using both candidate genes and random DNA markers
on a panel of 2-generation families in which
preeclampsia was rigorously defined. No evidence
was found for linkage to the HLA region or to
several genes implicated in the pathogenesis of
hypertension, e.g., pronatriodilatin (108780),
sodium-hydrogen ion antiporter (107310),
mineralocorticoid receptor (600983),
or glucocorticoid receptor (138040).
Van Meter and Weaver
(1993) commented on the study of Hayward
et al. (1992). See 106150.0001
for information concerning the association of
preeclampsia with a met235-to-thr mutation of the
angiotensin gene (AGT), which maps to 1q.
Harrison et al.
(1997) reported results of a genomewide linkage
search for preeclampsia/eclampsia (PEE)
susceptibility genes, using 15 informative
pedigrees. The 2.8-cM region between D4S450 and
D4S610 on 4q was identified as a strong candidate
region for a PEE susceptibility locus. The maximum
multipoint lod score within this interval was 2.9.
Analysis of markers in the region affected-member
method also supported the possibility of a
susceptibility locus in this region.
Sohda et al. (1997)
studied the 677C-T polymorphism of the
methylenetetrahydrofolate reductase gene (MTHFR;
236250.0003)
in preeclampsia. They found an increased frequency
of the 677T allele and the 677T homozygous genotype
in patients as compared with controls. The 677T
variant of MTHFR had been identified as a risk
factor in vascular disease in other studies.
See NOS3 (163729)
for a discussion of the possible role of
endothelial nitric oxide synthetase in the
pathogenesis of pregnancy-induced hypertension and
a study by Arngrimsson et al.
(1997) providing evidence for a preeclampsia
susceptibility locus in the region of 7q36 encoding
the NOS3 gene.
Thornton and Macdonald
(1999) performed a cohort study of female twins
with information on hypertensive diseases of
pregnancy obtained by questionnaire screening, and
verified the diagnosis from hospital or general
practitioner records. Self-reported preeclampsia
was found to have a heritability of 0.221 and
nonproteinuric hypertension of 0.198. However, none
of the pairs who were self-reported as concordant
for preeclampsia was confirmed from hospital
records. Using hospital records, the heritability
of preeclampsia was 0.0 and that for nonproteinuric
hypertension was 0.375. Using a model treating
preeclampsia as a separate disease from
nonproteinuric hypertension, and assuming that the
next pair identified was both monozygotic and
concordant for preeclampsia, the estimated
heritability of preeclampsia remained at 0.0. Using
a threshold model in which nonproteinuric
hypertension was treated as a mild form of
preeclampsia, heritability was estimated at 0.247.
They concluded that neither nonproteinuric
hypertension nor preeclampsia is inherited in a
simple mendelian fashion, and that the genetic
contribution to the multifactorial inheritance of
these 2 traits is smaller than hitherto believed.
-
SEE ALSO
- Anonymous (1980)
REFERENCES
- 1. Anonymous :
- Inheriting pre-eclampsia.
(Editorial) Brit. Med. J. 1:
1557-1558, 1980.
- 2. Anonymous :
- Genetic control of pre-eclampsia.
(Editorial) Lancet I: 634-635,
1980.
- 3. Anonymous :
- Genetics of pre-eclampsia.
(Editorial) Lancet II: 778,
1988.
PubMed ID : 2901618
- 4. Arngrimsson, R.;
Bjornsson, S.; Geirsson, R. T.; Bjornsson, H.;
Walker, J. J.; Snaedal, G. :
- Genetic and familial predisposition
to eclampsia and pre-eclampsia in a defined
population. Brit. J. Obstet.
Gynaec. 97: 762-769, 1990.
PubMed ID : 2242360
- 5. Arngrimsson, R.;
Hayward, C.; Nadaud, S.; Baldursdottir, A.;
Walker, J. J.; Liston, W. A.; Bjarnadottir, R.
I.; Brock, D. J. H.; Geirsson, R. T.; Connor, J.
M.; Soubrier, F. :
- Evidence for a familial
pregnancy-induced hypertension locus in the
eNOS-gene region. Am. J. Hum.
Genet. 61: 354-362, 1997.
PubMed ID : 9311740
- 6. Chesley, L. C.;
Annitto, J. E.; Cosgrove, R. A. :
- The familial factor in toxemia of
pregnancy. Obstet. Gynec. 32:
303-311, 1968.
PubMed ID : 5742111
- 7. Chesley, L. C.;
Cooper, D. W. :
- Genetics of hypertension in
pregnancy: possible single gene control of
pre-eclampsia and eclampsia in the descendants
of eclamptic women. Brit. J.
Obstet. Gynaec. 93: 898-908, 1986.
PubMed ID : 3768285
- 8. Cooper, D. W.;
Hill, J. A.; Chesley, L. C.; Bryans, C. I.
:
- Genetic control of susceptibility to
eclampsia and miscarriage. Brit. J.
Obstet. Gynaec. 95: 644-653, 1988.
PubMed ID : 3415930
- 9. Cooper, D. W.;
Liston, W. A. :
- Genetic control of severe
pre-eclampsia. J. Med. Genet.
16: 409-416, 1979.
PubMed ID : 537013
- 10. Davey, D. A.;
MacGillivray, I. :
- The classification and definition of
the hypertensive disorders of
pregnancy. Am. J. Obstet.
Gynec. 158: 892-898, 1988.
PubMed ID : 3364501
- 11. Fisher, K. A.;
Luger, A.; Spargo, B. H.; Lindheimer, M. D.
:
- Hypertension in pregnancy:
clinical-pathological correlations and remote
prognosis. Medicine 60:
267-276, 1981.
PubMed ID : 7242320
- 12. Harrison, G.
A.; Humphrey, K. E.; Jones, N.; Badenhop, R.;
Guo, G.; Elakis, G.; Kaye, J. A.; Turner, R. J.;
Grehan, M.; Wilton, A. N.; Brennecke, S. P.;
Cooper, D. W. :
- A genomewide linkage study of
preeclampsia/eclampsia reveals evidence for a
candidate region on 4q. Am. J. Hum.
Genet. 60: 1158-1167, 1997.
PubMed ID : 9150163
- 13. Hayward, C.;
Livingstone, J.; Holloway, S.; Liston, W. A.;
Brock, D. J. H. :
- An exclusion map for pre-eclampsia:
assuming autosomal recessive
inheritance. Am. J. Hum.
Genet. 50: 749-757, 1992.
PubMed ID : 1550119
- 14. Humphries, J.
O. :
- Occurrence of hypertensive toxemia
of pregnancy in mother-daughter pairs.
Bull. Johns Hopkins Hosp. 107: 271-277,
1960.
- 15. Kilpatrick, D.
C.; Liston, W. A.; Gibson, F.; Livingstone, J.
:
- Association between susceptibility
to pre-eclampsia within families and HLA
DR4. Lancet II: 1063-1065,
1989.
PubMed ID : 2572795
- 16. Liston, W. A.;
Kilpatrick, D. C. :
- Is genetic susceptibility to
pre-eclampsia conferred by homozygosity for the
same single recessive gene in mother and
fetus? Brit. J. Obstet.
Gynaec. 98: 1079-1086, 1991.
PubMed ID : 1760418
- 17. Sohda, S.;
Arinami, T.; Hamada, H.; Yamada, N.; Hamaguchi,
H.; Kubo, T. :
- Methylenetetrahydrofolate reductase
polymorphism and pre-eclampsia. J.
Med. Genet. 34: 525-526, 1997.
PubMed ID : 9192280
- 18. Thornton, J.
G.; Macdonald, A. M. :
- Twin mothers, pregnancy hypertension
and pre-eclampsia. Brit. J. Obstet.
Gynaec. 106: 570-575, 1999.
PubMed ID : 10426615
- 19. Van Meter, T.
D.; Weaver, D. D. :
- Concerns about the genetics of
pre-eclampsia. (Letter) Am. J. Hum.
Genet. 52: 1012-1013, 1993.
PubMed ID : 8488831
- 20. Wilton, A. N.;
Cooper, D. W.; Brennecke, S. P.; Bishop, S. M.;
Marshall, P. :
- Absence of close linkage between
maternal genes for susceptibility to
pre-eclampsia/eclampsia and HLA
DR-beta. Lancet 336: 653-657,
1990.
PubMed ID : 1975853
CLINICAL
SYNOPSIS
View
Clinical Synopsis Entry
Victor A. McKusick - updated : 9/8/1999
Victor A. McKusick - updated : 9/24/1997
Victor A. McKusick - updated : 9/8/1997
Victor A. McKusick - updated : 6/16/1997
Victor A. McKusick : 6/2/1986
EDIT HISTORY
carol : 9/20/1999
jlewis : 9/17/1999
terry : 9/8/1999
terry : 11/10/1997
terry : 9/30/1997
terry : 9/24/1997
mark : 9/10/1997
mark : 9/10/1997
mark : 9/8/1997
terry : 6/23/1997
terry : 6/16/1997
mark : 1/22/1996
joanna : 1/15/1996
mimadm : 5/10/1995
carol : 7/29/1994
davew : 7/18/1994
warfield : 4/21/1994
carol : 7/1/1993
carol : 5/15/1992
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