Genetic analysis of insulin-like growth factor II and HLA-G in pre-eclampsia

Pre-eclampsia (PE) is uniquely a disease of pregnancy and is the major caus e of foetal and maternal morbidity and mortality. Epidemiological studies s how that PE is highly heritable, with a high incidence in all populations. The underlying pathology indicates that absent or shallow invasion of foeta l trophoblasts into maternal arteries is a feature of true PE. The objectiv e of this study was to determine the genetic factors influencing PE. A larg e number of mother-father-baby trios were collected in which the first preg nancy was complicated by severe PE. After careful examination of the epidem iology and pathology of the disease, two plausible candidate genes, namely insulin-like growth factor II (IGF-II) and HLA-G, were analysed for associa tion with PE. No association was found between a commonly occurring polymor phism in IGF-II and PE. Three polymorphisms in HLA-G were analysed in the s ample cohorts. No association was found between three polymorphisms in HLA- G and PE. However, the frequency of the HLA-G insertion/deletion polymorphi sm in exon 8 deviated significantly from Hardy-Weinberg expectations in PE off-spring, reflecting an excess of heterozygotes for these polymorphisms i n PE offspring. The significance of this deviation is not clear and further genetic analysis will be necessary to confirm this finding and to explore further the candidacy of HLA-G in PE.