The Relationship in Japanese Infants between a Genetic Polymorphism in the Promoter Region of the Insulin-Like Growth Factor I Gene and the Plasma Level

Kinoshita, Yumiko; Kizaki, Zenro; Ishihara, Yasunori; Nakajima, Hisakazu; Adachi, Shinsuke; Kosaka, Kitaro; Kinugasa, Akihiko; Sugimoto, Tohru

doi:10.1159/000101062

Cited by 7 publications

(14 citation statements)

References 21 publications

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“…In adults, conflicting results have been reported with respect to the influence of the 192 bp allele on circulating IGF-I concentrations [7,15,48,49]. A recent study in 160 Japanese neonates did not find an association with IGF-I levels, which were, however, not measured in cord plasma but at day 5 after birth [50]. This finding is in line with our results.…”

Section: Discussionsupporting

confidence: 90%

Influence of Polymorphisms in Genes Encoding for Insulin-Like Growth Factor (IGF)-I, Insulin, and IGF-Binding Protein (IGFBP)-3 on IGF-I, IGF-II, and IGFBP-3 Levels in Umbilical Cord Plasma

Landmann¹,

Kollerits

Kreuder

et al. 2012

Horm Res Paediatr

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Background/Aims: In postnatal life, polymorphisms in the promoter region of IGFBP3 were associated with insulin-like growth factor binding protein (IGFBP)-3 plasma levels. Whether these associations exist in utero has not been studied yet. Polymorphisms in the IGF1 promoter (polymorphic CA-repeat) and the insulin gene variable number tandem repeats locus (INS VNTR) are further polymorphisms of interest, because associations with birth weight have been reported. We aimed to investigate associations between polymorphisms in the promoter regions of IGF1 (wild type 192 bp), IGFBP3 (rs2854744; rs13241830), and INS VNTR (rs689) with cord plasma levels of IGF-I, IGF-II, and IGFBP-3. Methods: We measured IGF-I, IGF-II, and IGFBP-3 concentrations in cord blood from 677 neonates and genotyped the selected polymorphisms. Results: Carriers of the minor allele of both polymorphisms in the IGFBP3 gene had, on average, 4–5% lower IGFBP-3 levels per copy of the respective minor allele (p = 0.002 and p = 0.028) when compared to wild type carriers. The IGF1 promoter and the INS VNTR polymorphisms were not associated with IGF-I, IGF-II, or IGFBP-3 levels. Conclusions: Our data show associations of cord plasma IGFBP-3 levels and the IGFBP3 gene variants but not of IGF1 promoter and INS VNTR polymorphisms with IGF-I, IGF-II, or IGFBP-3 levels in utero.

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Section: Discussionsupporting

confidence: 90%

Influence of Polymorphisms in Genes Encoding for Insulin-Like Growth Factor (IGF)-I, Insulin, and IGF-Binding Protein (IGFBP)-3 on IGF-I, IGF-II, and IGFBP-3 Levels in Umbilical Cord Plasma

Landmann¹,

Kollerits

Kreuder

et al. 2012

Horm Res Paediatr

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“…As the head circumference associations have also been demonstrated by Arends et al [3] in a selected, smaller population, we consider the observed head circumference associations as real. The association between gestational age and the –G1245A SNP is new, but many studies [16, 19,41,42,43,44] have investigated the association between the –841/192 bp VNTR and birth size. That gestational age might be an explanatory factor in these, sometimes, conflicting associations, is biologically plausible.…”

Section: Discussionmentioning

confidence: 99%

Birth Size, Postnatal Growth and Growth during Growth Hormone Treatment in Small-for-Gestational-Age Children: Associations with <i>IGF1</i> Gene Polymorphisms and Haplotypes?

Ester

Meurs²,

Arends³

et al. 2009

Horm Res Paediatr

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Background: Short small-for-gestational-age (SGA) children experience pre- and postnatal growth restriction, which might be influenced by polymorphisms in the IGF1 gene. The well-known –841(CA)_n/192 bp polymorphism has been associated with birth size and cardiovascular disease. Aims: To determine whether birth size, postnatal growth and growth during growth hormone (GH) treatment, were associated with IGF1 gene polymorphisms and haplotypes. Methods: 201 short SGA children were investigated for four IGF1 gene polymorphisms in the promoter (–G1245A, –841(CA)_n), intron 2 (+3703(CT)_n) and 3UTR (+A1830G). Spontaneous growth and growth during GH treatment were studied. Results: The –1245 A allele was identified as a marker-allele for the well-known –841(CA)_n/non-192 bp allele, both part of haplotype 2. The –1245 A allele was not associated with head circumference at birth, but was associated with a postnatal 0.3 SDS smaller head circumference at age 1–3. The –1245 A allele was also associated with a 1-week shorter gestational age which explained the association with a smaller absolute birth size. No associations were found with gestational age-adjusted birth size, height and weight SDS during postnatal life and with growth during GH treatment. Conclusions: The –G1245A SNP appeared to be a marker for the well-known –841(CA)_n/192 bp polymorphism. Haplotype 2, of which the –1245 A allele was the marker, was associated with a smaller head circumference SDS during spontaneous postnatal growth, but not during GH treatment.

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“…Several have examined the effect of the promoter CA di-nucleotide repeat polymorphism and relatively few have studied the other two polymorphisms in relation to fetal growth. These studies have reported conflicting results on the associations between the di-nucleotide repeat polymorphisms and IGF-1 levels or birth size [12,[14][15][16][17] .…”

mentioning

confidence: 99%

Di-Nucleotide Repeat Polymorphisms of the Insulin-Like Growth Factor-1 Gene and Their Association with IGF-1, Insulin-Like Growth Factor-Binding Protein-1 and Birth Size in a Sri-Lankan Cohort

et al. 2010

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Background: Insulin-like growth factor (IGF)-I is implicated in fetal growth. Ethnic variations of IGF-1 have also been suggested. Di-nucleotide repeat polymorphisms of the IGF-1 gene or their association with IGF-1 levels and birth size have not been studied in Sri Lankans. Objectives: To describe IGF-1 di-nucleotide repeat polymorphisms and their association with IGF-1 and IGF-binding protein (IGFBP)-1 levels and birth size in a cohort of Sri Lankans. Methods: A cross-sectional study on 200 mother-newborn pairs was carried out. Maternal and cord blood levels of IGF-1 and IGFBP-1 were measured by enzyme-linked immunosorbent assay. Three di-nucleotide repeat polymorphisms of the IGF-1 gene [cytosine-adenine (CA) repeats in the promoter and 3′ regions and intron 2 cytosine-thymine (CT) repeat] were studied using PCR amplification and fragment analysis. Results:Cord blood IGFBP-1 levels correlated negatively with birth weight (p < 0.01) and crown-heel length (p < 0.05). Wild-type alleles of the CA repeat polymorphisms differed from those reported in other populations. Newborn and maternal intron 2 CT repeat polymorphism showed a significant effect on birth weight (p < 0.01 and p < 0.001, respectively), crown-heel length (p < 0.01) and head circumference (p < 0.01 and p < 0.05, respectively). Promoter region CA repeat polymorphism and intron 2 CT repeat polymorphism in the newborns were significantly (p < 0.05) associated with cord blood IGF-1 levels. Almost all these effects were limited to primiparous pregnancies. Conclusions: In Sri Lankans intron 2 CT repeat polymorphism of the IGF-1 gene appears to be a significant contributor to IGF-1 levels and birth size in primiparous pregnancies.

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The Relationship in Japanese Infants between a Genetic Polymorphism in the Promoter Region of the Insulin-Like Growth Factor I Gene and the Plasma Level

Cited by 7 publications

References 21 publications

Influence of Polymorphisms in Genes Encoding for Insulin-Like Growth Factor (IGF)-I, Insulin, and IGF-Binding Protein (IGFBP)-3 on IGF-I, IGF-II, and IGFBP-3 Levels in Umbilical Cord Plasma

Influence of Polymorphisms in Genes Encoding for Insulin-Like Growth Factor (IGF)-I, Insulin, and IGF-Binding Protein (IGFBP)-3 on IGF-I, IGF-II, and IGFBP-3 Levels in Umbilical Cord Plasma

Birth Size, Postnatal Growth and Growth during Growth Hormone Treatment in Small-for-Gestational-Age Children: Associations with <i>IGF1</i> Gene Polymorphisms and Haplotypes?

Di-Nucleotide Repeat Polymorphisms of the Insulin-Like Growth Factor-1 Gene and Their Association with IGF-1, Insulin-Like Growth Factor-Binding Protein-1 and Birth Size in a Sri-Lankan Cohort

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