Associations of IGF2 ApaI RFLP and INS VNTR class I allele size with obesity

O’Dell, Sandra D.; Bujac, Sarah R.; Miller, George; Day, Ian N.M.

doi:10.1038/sj.ejhg.5200381

Cited by 44 publications

(29 citation statements)

References 29 publications

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“…Conversely, it has also been shown that class III homozygote children and young adults may have a greater BMI than class I carriers (4,6). By contrast, we found no association between INS VNTR class as inferred by the Ϫ23Hph1 genotype and BMI in 7,999 middle-aged men and women, confirming previous reports based on middle-aged study participants (7,22).…”

Section: Discussionsupporting

confidence: 36%

INS VNTR Class Genotype and Indexes of Body Size and Obesity

et al. 2005

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The relevance of the insulin gene (INS) variable number tandem repeat (VNTR) polymorphism to indexes of body size and adult obesity is inconclusive. Given the equivocal reports on the association between the VNTR class genotype at the insulin gene locus and indexes of body size and obesity, we assessed these associations in a series of cohort studies based on 7,999 middle-aged men and women. We found no convincing evidence that INS VNTR class genotype was associated with indexes of body size and adult obesity. These data suggest that INS VNTR class is not an important determinant of size and body weight regulation in middle-aged men and women. Diabetes 54:2812-2815, 2005 E xperimental and observational studies have suggested that insulin signaling is involved in regulation of somatic growth and body weight (1). The variable number tandem repeat (VNTR) polymorphism, lying 396 base pairs 5Ј to the insulin gene on chromosome 11p15.5, is thought to influence insulin expression (2,3). This minisatellite polymorphism has also been associated with altered expression of the nearby IGF-II, a key regulator of fetal growth and development (4,5). Collectively, observational studies have reported conflicting associations between the INS VNTR class genotype and indexes of body size in childhood and obesity (4,6 -8). Importantly, the relevance of INS VNTR class to indexes of body size and obesity in adults is also inconclusive. Given these equivocal results, we assessed the association between INS VNTR class genotype and indexes of body size and adult obesity in a series of cohort studies based on 7,999 middle-aged men and women. RESEARCH DESIGN AND METHODSWe used data from the Norfolk cohort of the European Prospective Investigation into Cancer (EPIC) and the Ely Study. EPIC is an ongoing prospective cohort study of ϳ25,000 people aged 45-75, resident in Norfolk, and recruited from general practice registers between 1993 and 1997 (9). It is an ethnically homogeneous Caucasian population. These participants completed a health examination. In January 1998, we invited the cohort for a second health examination, and 15,786 people had attended by October 2000. All participants gave informed consent. Details of recruitment, anthropometric measurements, and health examinations following standardized protocols have been published (9). All participants completed a detailed health and lifestyle questionnaire, which included a question on birth weight. A D-loop nonstretch fiberglass tape was used for the head circumference measures. DNA was extracted from the 15,786 whole blood/EDTA samples (Whatman Biosciences, Ely, U.K.) taken at the second health examination. BMI was calculated from the weight and height measures.For the purposes of this analysis, we examined data from two subcohorts of the 15,786 EPIC study participants who attended the second health examination (9). EPIC1 comprises 3,744 participants with fully arrayed DNA available for genotyping. EPIC2 is a random sample of 5,000 participants who were free of baseline disease (ca...

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Section: Discussionsupporting

confidence: 36%

INS VNTR Class Genotype and Indexes of Body Size and Obesity

et al. 2005

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“…In lung, the most variant genes include integrin-␤2, which has been shown to predispose individuals to recurrent bacterial infections (16,20), and antileukoproteinase, which is involved in several chronic and acute diseases of the respiratory tract (4,35). In liver, the most variant genes include insulin-like growth factor 2, a putative susceptibility factor for obesity (9,12,32); fibrinogen-␥, defects of which are a cause of thrombophilia (26,27); and hepatic lipase, a complete deficiency of which causes coronary atherosclerosis and premature dyslipidemia (17,33). Each of the other 13 tissue types contains samples from less than 3 different individuals.…”

Section: Housekeeping or Maintenance Genes And Their Tissuespecific Ementioning

confidence: 99%

A compendium of gene expression in normal human tissues

Hsiao¹,

Dangond

Yoshida³

et al. 2001

Physiological Genomics

386

345

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This study creates a compendium of gene expression in normal human tissues suitable as a reference for defining basic organ systems biology. Using oligonucleotide microarrays, we analyze 59 samples representing 19 distinct tissue types. Of ∼7,000 genes analyzed, 451 genes are expressed in all tissue types and designated as housekeeping genes. These genes display significant variation in expression levels among tissues and are sufficient for discerning tissue-specific expression signatures, indicative of fundamental differences in biochemical processes. In addition, subsets of tissue-selective genes are identified that define key biological processes characterizing each organ. This compendium highlights similarities and differences among organ systems and different individuals and also provides a publicly available resource (Human Gene Expression Index, the HuGE Index, http://www.hugeindex.org ) for future studies of pathophysiology.

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“…16,17 As impaired fetal growth is a risk factor for adult metabolic diseases, 18 genes like IGF2 are attractive candidates to explain susceptibility to disorders such as T2D and obesity, and accordingly several association studies have been conducted. [19][20][21][22][23][24][25][26][27][28][29] In a sample of British middle-aged men, the minor allele of the 820G4A (ApaI) single nucleotide polymorphism (SNP) located in the 3 0 untranslated region of the IGF2 gene was associated with lower body mass, lower body mass index (BMI) and higher IGF2 levels. 20,21 Although the association with lower BMI was replicated in an Israeli sample, 22 several studies failed to confirm this.…”

Section: Introductionmentioning

confidence: 99%

“…[19][20][21][22][23][24][25][26][27][28][29] In a sample of British middle-aged men, the minor allele of the 820G4A (ApaI) single nucleotide polymorphism (SNP) located in the 3 0 untranslated region of the IGF2 gene was associated with lower body mass, lower body mass index (BMI) and higher IGF2 levels. 20,21 Although the association with lower BMI was replicated in an Israeli sample, 22 several studies failed to confirm this. [23][24][25] Moreover, a study in American participants even showed that minor allele carriers had a greater fat body mass.…”

Section: Introductionmentioning

confidence: 99%

Parent-of-origin specific linkage and association of the IGF2 gene region with birth weight and adult metabolic risk factors

et al. 2009

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Objective: The maternally imprinted insulin-like growth factor 2 (IGF2) gene is an important fetal growth factor and is also suggested to have postnatal metabolic effects. In this study, we examined whether common polymorphisms in IGF2 (6815_6819delAGGGC, 1156T4C and 820G4A (ApaI)) and a microsatellite marker in the close vicinity of IGF2 were linked to or associated with birth weight and adult metabolic risk factors. Design and participants: Polymorphisms were genotyped in 199 monozygotic complete twin pairs, 109 dizygotic complete twin pairs, 15 single twins, 231 mothers and 228 fathers recruited from the East Flanders Prospective Twin Survey. Conventional and parent-of-origin specific linkage and association analyses were carried out with birth weight, adult body height and parameters quantifying obesity, insulin sensitivity and dyslipidaemia measured at adult age (mean age 25 years). Results: In the parent-of-origin specific association analysis, in which only the paternally inherited allele was incorporated, the 1156T4C SNP (single nucleotide polymorphism) showed significant association with IGF-binding protein 1 (IGFBP1) levels (T and C (mean (95% CI)): 13.2 (12.1-14.3) and 16.2 (14.6-18.0) ng ml À1 , P ¼ 0.002). No linkage was observed in either the conventional or in the parent-of-origin specific linkage analysis. Conclusion: This study suggests that paternally inherited alleles of a common polymorphism in the IGF2 gene affect IGFBP1 levels.

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Associations of IGF2 ApaI RFLP and INS VNTR class I allele size with obesity

Abstract: Body mass index (BMI) is

Cited by 44 publications

References 29 publications

INS VNTR Class Genotype and Indexes of Body Size and Obesity

INS VNTR Class Genotype and Indexes of Body Size and Obesity

A compendium of gene expression in normal human tissues

Parent-of-origin specific linkage and association of the IGF2 gene region with birth weight and adult metabolic risk factors

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