期刊
JOURNAL OF IMMUNOLOGY
卷 192, 期 11, 页码 5069-5073出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1400577
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资金
- Wellcome Trust [090108/Z/09/Z, 085992/Z/08/Z]
- British Heart Foundation [PG/09/077/27964]
- Centre for Trophoblast Research
- Frederick National Laboratory for Cancer Research [HHSN261200800001E]
- Intramural Research Program of National Institutes of Health, Frederick National Laboratory, Center for Cancer Research
- British Heart Foundation [PG/09/077/27964] Funding Source: researchfish
- Wellcome Trust [090108/Z/09/Z, 085992/Z/08/Z] Funding Source: Wellcome Trust
Human birth weight is subject to stabilizing selection; babies born too small or too large are less likely to survive. Particular combinations of maternal/fetal immune system genes are associated with pregnancies where the babies are <= 5th birth weight centile, specifically an inhibitory maternal KIR AA genotype with a paternally derived fetal HLA-C2 ligand. We have now analyzed maternal KIR and fetal HLA-C combinations at the opposite end of the birth weight spectrum. Mother/baby pairs (n = 1316) were genotyped for maternal KIR as well as fetal and maternal HLA-C. Presence of a maternal-activating KIR2DS1 gene was associated with increased birth weight in linear or logistic regression analyses of all pregnancies >5th centile (p = 0.005, n = 1316). Effect of KIR2DS1 was most significant in pregnancies where its ligand, HLA-C2, was paternally but not maternally inherited by a fetus (p = 0.005, odds ratio = 2.65). Thus, maternal KIR are more frequently inhibitory with small babies but activating with big babies. At both extremes of birth weight, the KIR associations occur when their HLA-C2 ligand is paternally inherited by a fetus. We conclude that the two polymorphic immune gene systems, KIR and HLA-C, contribute to successful reproduction by maintaining birth weight between two extremes with a clear role for paternal HLA.
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