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Common polymorphism in H19 associated with birthweight and cord blood IGF-II levels in humans.

Petry CJ, Ong KK, Barratt BJ, Wingate D, Cordell HJ, Ring SM, Pembrey ME, Reik W, Todd JA, Dunger DB, ALSPAC Study Te - BMC Genet. (2005)

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Paediatrics, University of Cambridge, Addenbrooke's Hospital Level 8, Box 116, Cambridge CB2 2QQ, UK. cjp1002@mole.bio.cam.ac.uk

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.

Conclusion: 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.

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Birthweight SD score (A) and cord blood IGF-II levels at birth (B) in the ALSPAC cohort, by mother's H19 2992 genotype, and stratified by birth order ("Primip" = mother's first child; "Non-primip" = second or subsequent child). Mean ± 95% CI. First-born infants had lower birthweights than infants of subsequent pregnancies (Ref. 5). Associations with mother's genotype (CC vs. T* [CT or TT]) were only seen in first pregnancies.
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Figure 1: Birthweight SD score (A) and cord blood IGF-II levels at birth (B) in the ALSPAC cohort, by mother's H19 2992 genotype, and stratified by birth order ("Primip" = mother's first child; "Non-primip" = second or subsequent child). Mean ± 95% CI. First-born infants had lower birthweights than infants of subsequent pregnancies (Ref. 5). Associations with mother's genotype (CC vs. T* [CT or TT]) were only seen in first pregnancies.

Mentions: The H19 2992 SNP was subsequently genotyped in DNA samples collected from mothers and fathers, for which the family relationships had been validated by genotyping. H19 2992 genotype in mothers, but not in fathers, showed associations with size at birth, and also with cord blood IGF-II levels (Table 2). Mother's H19 2992 genotype associations were independent of mother's pre-pregnancy weight and height (additive models: birthweight: P = 0.001; cord IGF-II levels: P = 0.0005). The association between mother's H19 2992 genotype and IGF-II levels appeared to vary with mother's parity (birth order), being evident only in first pregnancies (Figure 1), although formal test for interaction did not reach significance (P = 0.06). When both mother's and offspring's genotypes were included in a multivariate analysis, birthweight was significantly associated with both mother's H19 2992 genotype (P < 0.05) and also offspring's H19 2992 genotype (P = 0.01), suggesting that there were separate effects of mother's and offspring's genotype on birthweight.


Common polymorphism in H19 associated with birthweight and cord blood IGF-II levels in humans.

Petry CJ, Ong KK, Barratt BJ, Wingate D, Cordell HJ, Ring SM, Pembrey ME, Reik W, Todd JA, Dunger DB, ALSPAC Study Te - BMC Genet. (2005)

Birthweight SD score (A) and cord blood IGF-II levels at birth (B) in the ALSPAC cohort, by mother's H19 2992 genotype, and stratified by birth order ("Primip" = mother's first child; "Non-primip" = second or subsequent child). Mean ± 95% CI. First-born infants had lower birthweights than infants of subsequent pregnancies (Ref. 5). Associations with mother's genotype (CC vs. T* [CT or TT]) were only seen in first pregnancies.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC1140752&req=5

Figure 1: Birthweight SD score (A) and cord blood IGF-II levels at birth (B) in the ALSPAC cohort, by mother's H19 2992 genotype, and stratified by birth order ("Primip" = mother's first child; "Non-primip" = second or subsequent child). Mean ± 95% CI. First-born infants had lower birthweights than infants of subsequent pregnancies (Ref. 5). Associations with mother's genotype (CC vs. T* [CT or TT]) were only seen in first pregnancies.
Mentions: The H19 2992 SNP was subsequently genotyped in DNA samples collected from mothers and fathers, for which the family relationships had been validated by genotyping. H19 2992 genotype in mothers, but not in fathers, showed associations with size at birth, and also with cord blood IGF-II levels (Table 2). Mother's H19 2992 genotype associations were independent of mother's pre-pregnancy weight and height (additive models: birthweight: P = 0.001; cord IGF-II levels: P = 0.0005). The association between mother's H19 2992 genotype and IGF-II levels appeared to vary with mother's parity (birth order), being evident only in first pregnancies (Figure 1), although formal test for interaction did not reach significance (P = 0.06). When both mother's and offspring's genotypes were included in a multivariate analysis, birthweight was significantly associated with both mother's H19 2992 genotype (P < 0.05) and also offspring's H19 2992 genotype (P = 0.01), suggesting that there were separate effects of mother's and offspring's genotype on birthweight.

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Paediatrics, University of Cambridge, Addenbrooke's Hospital Level 8, Box 116, Cambridge CB2 2QQ, UK. cjp1002@mole.bio.cam.ac.uk

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.

Conclusion: 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.

Show MeSH
Related in: MedlinePlus