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Associations between paternally transmitted fetal IGF2 variants and maternal circulating glucose concentrations in pregnancy.

Petry CJ, Seear RV, Wingate DL, Manico L, Acerini CL, Ong KK, Hughes IA, Dunger DB - Diabetes (2011)

Bottom Line: Associations were tested between inferred parent-of-origin fetal alleles, z scores of maternal glucose concentrations 60 min. after an oral glucose load performed at week 28 of pregnancy, and offspring birth weights.Using the minimum P value test, paternally transmitted fetal IGF2 polymorphisms were associated with maternal glucose concentrations; specifically, paternally transmitted fetal rs6578987 (P = 0.006), rs680 (P = 0.01), rs10770125 (P = 0.0002), and rs7924316 (P = 0.01) alleles were associated with increased maternal glucose concentrations in the third trimester of pregnancy and placental IGF-II contents at birth (P = 0.03).Polymorphic variation in paternally transmitted fetal IGF2 is associated with increased maternal glucose concentrations in pregnancy and could potentially alter the risk of gestational diabetes in the mother.

View Article: PubMed Central - PubMed

Affiliation: Department of Paediatrics, University of Cambridge, Cambridge, UK. cjp1002@cam.ac.uk

ABSTRACT

Objective: To test the hypothesis that polymorphic variation in the paternally transmitted fetal IGF2 gene is associated with maternal glucose concentrations in the third trimester of pregnancy.

Research design and methods: A total of 17 haplotype tag single nucleotide polymorphisms in the IGF2 gene region were genotyped in 1,160 mother/partner/offspring trios from the prospective Cambridge Baby Growth Study (n = 845 trios) and the retrospective Cambridge Wellbeing Study (n = 315 trios) (3,480 samples in total). Associations were tested between inferred parent-of-origin fetal alleles, z scores of maternal glucose concentrations 60 min. after an oral glucose load performed at week 28 of pregnancy, and offspring birth weights.

Results: Using the minimum P value test, paternally transmitted fetal IGF2 polymorphisms were associated with maternal glucose concentrations; specifically, paternally transmitted fetal rs6578987 (P = 0.006), rs680 (P = 0.01), rs10770125 (P = 0.0002), and rs7924316 (P = 0.01) alleles were associated with increased maternal glucose concentrations in the third trimester of pregnancy and placental IGF-II contents at birth (P = 0.03). In contrast, there were no associations between maternal glucose concentrations and maternal or maternally transmitted fetal IGF2 genotypes.

Conclusions: Polymorphic variation in paternally transmitted fetal IGF2 is associated with increased maternal glucose concentrations in pregnancy and could potentially alter the risk of gestational diabetes in the mother. The association may be at least partially mediated by changes in placental IGF2 expression.

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Related in: MedlinePlus

Schematic diagram of the region of chromosome 11 genotyped in this study, showing the associated genes (IGF2, INS, and TH) and transcripts (IGF2, INS, TH, antisense IGF2, and INS-IGF2 readthrough transcript). Exons are shown as blocks. Chromosomal position based on National Center for Biotechnology Information Genome Reference Consortium Human genome build 36. (A high-quality color representation of this figure is available in the online issue.)
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Figure 1: Schematic diagram of the region of chromosome 11 genotyped in this study, showing the associated genes (IGF2, INS, and TH) and transcripts (IGF2, INS, TH, antisense IGF2, and INS-IGF2 readthrough transcript). Exons are shown as blocks. Chromosomal position based on National Center for Biotechnology Information Genome Reference Consortium Human genome build 36. (A high-quality color representation of this figure is available in the online issue.)

Mentions: A total of 17 IGF2 region (i.e., IGF2-INS-TH cluster) SNPs were selected based on the 11 haplotype tag SNPs identified by Rodríguez et al. (16), plus 6 SNPs from the Centre d'Etude du Polymorphisme Humain (CEU) population (Utah residents with ancestry from Northern and Western Europe) of the HapMap Project Build 36 using Haploview (17) (Hapmap accessed 19 January 2010). We force included the 11 Rodríguez et al. SNPs, using pairwise tagging r2 >0.8 and a minor allele frequency of at least 0.2 as the acceptance criteria (Fig. 1), and identified 5 haplotype blocks tagged by 14 SNPs (Table 3 and Supplementary Fig. 1). Three of the SNPs used by Rodríguez et al. were not required to define these haplotype blocks but were included for genotyping.


Associations between paternally transmitted fetal IGF2 variants and maternal circulating glucose concentrations in pregnancy.

Petry CJ, Seear RV, Wingate DL, Manico L, Acerini CL, Ong KK, Hughes IA, Dunger DB - Diabetes (2011)

Schematic diagram of the region of chromosome 11 genotyped in this study, showing the associated genes (IGF2, INS, and TH) and transcripts (IGF2, INS, TH, antisense IGF2, and INS-IGF2 readthrough transcript). Exons are shown as blocks. Chromosomal position based on National Center for Biotechnology Information Genome Reference Consortium Human genome build 36. (A high-quality color representation of this figure is available in the online issue.)
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3198064&req=5

Figure 1: Schematic diagram of the region of chromosome 11 genotyped in this study, showing the associated genes (IGF2, INS, and TH) and transcripts (IGF2, INS, TH, antisense IGF2, and INS-IGF2 readthrough transcript). Exons are shown as blocks. Chromosomal position based on National Center for Biotechnology Information Genome Reference Consortium Human genome build 36. (A high-quality color representation of this figure is available in the online issue.)
Mentions: A total of 17 IGF2 region (i.e., IGF2-INS-TH cluster) SNPs were selected based on the 11 haplotype tag SNPs identified by Rodríguez et al. (16), plus 6 SNPs from the Centre d'Etude du Polymorphisme Humain (CEU) population (Utah residents with ancestry from Northern and Western Europe) of the HapMap Project Build 36 using Haploview (17) (Hapmap accessed 19 January 2010). We force included the 11 Rodríguez et al. SNPs, using pairwise tagging r2 >0.8 and a minor allele frequency of at least 0.2 as the acceptance criteria (Fig. 1), and identified 5 haplotype blocks tagged by 14 SNPs (Table 3 and Supplementary Fig. 1). Three of the SNPs used by Rodríguez et al. were not required to define these haplotype blocks but were included for genotyping.

Bottom Line: Associations were tested between inferred parent-of-origin fetal alleles, z scores of maternal glucose concentrations 60 min. after an oral glucose load performed at week 28 of pregnancy, and offspring birth weights.Using the minimum P value test, paternally transmitted fetal IGF2 polymorphisms were associated with maternal glucose concentrations; specifically, paternally transmitted fetal rs6578987 (P = 0.006), rs680 (P = 0.01), rs10770125 (P = 0.0002), and rs7924316 (P = 0.01) alleles were associated with increased maternal glucose concentrations in the third trimester of pregnancy and placental IGF-II contents at birth (P = 0.03).Polymorphic variation in paternally transmitted fetal IGF2 is associated with increased maternal glucose concentrations in pregnancy and could potentially alter the risk of gestational diabetes in the mother.

View Article: PubMed Central - PubMed

Affiliation: Department of Paediatrics, University of Cambridge, Cambridge, UK. cjp1002@cam.ac.uk

ABSTRACT

Objective: To test the hypothesis that polymorphic variation in the paternally transmitted fetal IGF2 gene is associated with maternal glucose concentrations in the third trimester of pregnancy.

Research design and methods: A total of 17 haplotype tag single nucleotide polymorphisms in the IGF2 gene region were genotyped in 1,160 mother/partner/offspring trios from the prospective Cambridge Baby Growth Study (n = 845 trios) and the retrospective Cambridge Wellbeing Study (n = 315 trios) (3,480 samples in total). Associations were tested between inferred parent-of-origin fetal alleles, z scores of maternal glucose concentrations 60 min. after an oral glucose load performed at week 28 of pregnancy, and offspring birth weights.

Results: Using the minimum P value test, paternally transmitted fetal IGF2 polymorphisms were associated with maternal glucose concentrations; specifically, paternally transmitted fetal rs6578987 (P = 0.006), rs680 (P = 0.01), rs10770125 (P = 0.0002), and rs7924316 (P = 0.01) alleles were associated with increased maternal glucose concentrations in the third trimester of pregnancy and placental IGF-II contents at birth (P = 0.03). In contrast, there were no associations between maternal glucose concentrations and maternal or maternally transmitted fetal IGF2 genotypes.

Conclusions: Polymorphic variation in paternally transmitted fetal IGF2 is associated with increased maternal glucose concentrations in pregnancy and could potentially alter the risk of gestational diabetes in the mother. The association may be at least partially mediated by changes in placental IGF2 expression.

Show MeSH
Related in: MedlinePlus