title: Common polymorphism in H19 associated with birthweight and cord blood IGF-II levels in humans.
abstract: BACKGROUND
  Common genetic variation at genes that are imprinted and exclusively maternally expressed could explain the apparent maternal-specific inheritance of low birthweight reported in large family pedigrees. We identified ten single nucleotide polymorphisms (SNPs) in H19, and we genotyped three of these SNPs in families from the contemporary ALSPAC UK birth cohort (1,696 children, 822 mothers and 661 fathers) in order to explore associations with size at birth and cord blood IGF-II levels.
  
  
  RESULTS
  Both offspring's and mother's H19 2992C>T SNP genotypes showed associations with offspring birthweight (P = 0.03 to P = 0.003) and mother's genotype was also associated with cord blood IGF-II levels (P = 0.0003 to P = 0.0001). The offspring genotype association with birthweight was independent of mother's genotype (P = 0.01 to P = 0.007). However, mother's untransmitted H19 2992T allele was also associated with larger birthweight (P = 0.04) and higher cord blood IGF-II levels (P = 0.002), suggesting a direct effect of mother's genotype on placental IGF-II expression and fetal growth. The association between mother's untransmitted allele and cord blood IGF-II levels was more apparent in offspring of first pregnancies than subsequent pregnancies (P-interaction = 0.03). Study of the independent Cambridge birth cohort with available DNA in mothers (N = 646) provided additional support for mother's H19 2992 genotype associations with birthweight (P = 0.04) and with mother's glucose levels (P = 0.01) in first pregnancies.
  
  
  CONCLUSIONS
  The common H19 2992T allele, in the mother or offspring or both, may confer reduced fetal growth restraint, as indicated by associations with larger offspring birth size, higher cord blood IGF-II levels, and lower compensatory early postnatal catch-up weight gain, that are more evident among mother's smaller first-born infants.
authors.affiliation: Department of Paediatrics, University of Cambridge, Addenbrooke's Hospital Level 8, Box 116, Cambridge CB2 2QQ, UK. cjp1002@mole.bio.cam.ac.uk
authors.forename: Clive J
authors.initials: CJ
authors.lastname: Petry
authors.forename: Ken K
authors.initials: KK
authors.lastname: Ong
authors.forename: Bryan J
authors.initials: BJ
authors.lastname: Barratt
authors.forename: Diane
authors.initials: D
authors.lastname: Wingate
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Cordell
authors.forename: Susan M
authors.initials: SM
authors.lastname: Ring
authors.forename: Marcus E
authors.initials: ME
authors.lastname: Pembrey
authors.forename: Wolf
authors.initials: W
authors.lastname: Reik
authors.forename: John A
authors.initials: JA
authors.lastname: Todd
authors.forename: David B
authors.initials: DB
authors.lastname: Dunger
mesh_terms: D001724:Birth Weight; D005260:Female; D005312:Fetal Blood; D047109:Fetal Development / Q000235:genetics; D005838:Genotype; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000032:analysis*; D008297:Male; D010920:Placenta / Q000737:chemistry; D011110:Polymorphism, Genetic; D011247:Pregnancy; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics*
chemical_list: C094335:H19 long non-coding RNA; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D007335:Insulin-Like Growth Factor II