PMID- 18263639
OWN - NLM
STAT- MEDLINE
DCOM- 20080527
LR  - 20220331
IS  - 1460-2350 (Electronic)
IS  - 0268-1161 (Linking)
VI  - 23
IP  - 4
DP  - 2008 Apr
TI  - Association of maternal killer-cell immunoglobulin-like receptors and parental 
      HLA-C genotypes with recurrent miscarriage.
PG  - 972-6
LID - 10.1093/humrep/den011 [doi]
AB  - BACKGROUND: The natural killer (NK) cells at the site of placentation express 
      killer-cell immunoglobulin-like receptors (KIR) that can bind to human leukocyte 
      antigen (HLA)-C molecules on trophoblast cells. Both these gene systems are 
      polymorphic and an association of particular maternal KIR/fetal HLA-C genotypes 
      has been shown in pre-eclampsia. Pre-eclampsia and recurrent miscarriage (RM) 
      share the pathogenesis of defective placentation and therefore we have now 
      genotyped couples with RM. METHODS AND RESULTS: DNA was obtained from the male (n 
      = 67) and female (n = 95) partners of couples with three or more spontaneous 
      miscarriages and genotyped for HLA-C groups and 11 KIR genes using the 
      PCR-sequence-specific primer method (SSP). The frequency of the HLA-C2 group was 
      increased in both parents (reaching significance only in the male partners, P = 
      0.018) compared with a parous control population. The KIR gene frequencies of the 
      male partners were similar to controls, but the women had a high frequency of KIR 
      AA haplotypes that lack activating KIR. In particular, the activating KIR for 
      HLA-C2 groups (KIR2DS1) was significantly lower in these women (P = 0.00035, odds 
      ratio 2.63, confidence interval 1.54-4.49). CONCLUSIONS: This is the first report 
      to identify a genetic male factor that confers risk in RM. These findings support 
      the idea that successful placentation depends on the correct balance of NK cell 
      inhibition and activation in response to trophoblast.
FAU - Hiby, S E
AU  - Hiby SE
AD  - Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge 
      CB2 1QP, UK.
FAU - Regan, L
AU  - Regan L
FAU - Lo, W
AU  - Lo W
FAU - Farrell, L
AU  - Farrell L
FAU - Carrington, M
AU  - Carrington M
FAU - Moffett, A
AU  - Moffett A
LA  - eng
GR  - N01-CO-12400/CO/NCI NIH HHS/United States
GR  - British Heart Foundation/United Kingdom
GR  - Intramural NIH HHS/United States
GR  - Wellcome Trust/United Kingdom
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20080208
PL  - England
TA  - Hum Reprod
JT  - Human reproduction (Oxford, England)
JID - 8701199
RN  - 0 (HLA-C Antigens)
RN  - 0 (Receptors, KIR)
SB  - IM
MH  - Abortion, Habitual/*immunology
MH  - Female
MH  - Genotype
MH  - HLA-C Antigens/*genetics/immunology
MH  - Haplotypes
MH  - Humans
MH  - Male
MH  - Placentation/*immunology
MH  - Polymerase Chain Reaction
MH  - Pre-Eclampsia/immunology
MH  - Pregnancy
MH  - Receptors, KIR/*immunology
MH  - Trophoblasts/*immunology
EDAT- 2008/02/12 09:00
MHDA- 2008/05/28 09:00
CRDT- 2008/02/12 09:00
PHST- 2008/02/12 09:00 [pubmed]
PHST- 2008/05/28 09:00 [medline]
PHST- 2008/02/12 09:00 [entrez]
AID - den011 [pii]
AID - 10.1093/humrep/den011 [doi]
PST - ppublish
SO  - Hum Reprod. 2008 Apr;23(4):972-6. doi: 10.1093/humrep/den011. Epub 2008 Feb 8.