Limits...
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.

Show MeSH

Related in: MedlinePlus

Postnatal weight gain (change in weight SD score 0–3 years) in the ALSPAC cohort, by offspring's (A) or mother's (B) H19 2992 genotype, and stratified by birth order ("Primip" = mother's first child; "Non-primip" = second or subsequent child). Mean ± 95% CI. The overall association between weight gain and offspring genotype (CC vs. T* [CT or TT], P = 0.01; Table 5) was only apparent in first-born offspring.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC1140752&req=5

Figure 2: Postnatal weight gain (change in weight SD score 0–3 years) in the ALSPAC cohort, by offspring's (A) or mother's (B) H19 2992 genotype, and stratified by birth order ("Primip" = mother's first child; "Non-primip" = second or subsequent child). Mean ± 95% CI. The overall association between weight gain and offspring genotype (CC vs. T* [CT or TT], P = 0.01; Table 5) was only apparent in first-born offspring.

Mentions: 1,449 ALSPAC children were followed-up to age 3 years. Neither offspring nor parental H19 genotypes showed association with offspring body size at age 3 years (not shown). The apparent loss of T allele-related size advantage between birth and age 3 years was explained by slower rates of weight gain during this period (Table 5). As with birthweight and IGF-II levels, the H19 2992 genotype associations with postnatal weight gain were more apparent in offspring of first pregnancies (Figure 2).


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)

Postnatal weight gain (change in weight SD score 0–3 years) in the ALSPAC cohort, by offspring's (A) or mother's (B) H19 2992 genotype, and stratified by birth order ("Primip" = mother's first child; "Non-primip" = second or subsequent child). Mean ± 95% CI. The overall association between weight gain and offspring genotype (CC vs. T* [CT or TT], P = 0.01; Table 5) was only apparent in first-born offspring.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Postnatal weight gain (change in weight SD score 0–3 years) in the ALSPAC cohort, by offspring's (A) or mother's (B) H19 2992 genotype, and stratified by birth order ("Primip" = mother's first child; "Non-primip" = second or subsequent child). Mean ± 95% CI. The overall association between weight gain and offspring genotype (CC vs. T* [CT or TT], P = 0.01; Table 5) was only apparent in first-born offspring.
Mentions: 1,449 ALSPAC children were followed-up to age 3 years. Neither offspring nor parental H19 genotypes showed association with offspring body size at age 3 years (not shown). The apparent loss of T allele-related size advantage between birth and age 3 years was explained by slower rates of weight gain during this period (Table 5). As with birthweight and IGF-II levels, the H19 2992 genotype associations with postnatal weight gain were more apparent in offspring of first pregnancies (Figure 2).

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