A polymorphic CA repeat in the IGF‐I gene is associated with gender‐specific differences in body height, but has no effect on the secular trend in body height

Rietveld, Ingrid; Janssen, Joseph A M J L; Rossum, Elisabeth F.C. van; Houwing‐Duistermaat, Jeanine J.; Rivadeneira, Fernando; Hofman, Albert; Pols, Huibert A. P.; Duijn, Cornelia M. van; Lamberts, Steven W. J.

doi:10.1111/j.1365-2265.2004.02078.x

Cited by 77 publications

(73 citation statements)

References 26 publications

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“…Consistent with our findings, several studies examining female White Caucasian populations did not find an association between 5¢CA-19 and height [22][23][24] or BMI, 22,25 or between 5¢CA-20 and height. 23 No association between 5¢CA-19 and BMI was found for Hispanic or Chinese women (although among Chinese women 5¢CA-17 was associated with lower BMI).…”

supporting

confidence: 92%

“…23 No association between 5¢CA-19 and BMI was found for Hispanic or Chinese women (although among Chinese women 5¢CA-17 was associated with lower BMI). 25,26 In a study from the Netherlands (Rotterdam), women homozygous for either 5¢CA-19 or 5¢CA-20 were significantly heavier than other homozygotes.…”

mentioning

confidence: 94%

“…25,26 In a study from the Netherlands (Rotterdam), women homozygous for either 5¢CA-19 or 5¢CA-20 were significantly heavier than other homozygotes. 23 Another Netherlands (Amsterdam) study found that homozygous carriers of 5¢CA-19, 5¢CA-20 or 5¢CA-19/20 heterozygotes had significantly higher BMI than women with other genotypes, for one of two cohorts examined. 27 We did not investigate these allele groupings specifically, but, inconsistent with these results, grouping 5¢CA-19 and 20 alleles did not yield a significant association with weight or BMI when tested under a recessive model (data not shown).…”

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confidence: 97%

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Family-based association study of IGF1 microsatellites and height, weight, and body mass index

et al. 2010

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Height, weight, and body mass index (BMI) are partly heritable, known to be associated with chronic diseases, and are linked to circulating insulin-like growth factor I (IGF-I) concentrations. IGF-I concentrations are also partly heritable and thus genetic variation at IGF1 could influence height, weight, BMI and the risk of developing chronic diseases. Our objective was to examine the association of genetic variation at IGF1 with height, weight and BMI using a sample of premenopausal women. A familybased study design was used to investigate the association of three IGF1 CA repeat variants at 5¢ (5¢CA), intron 2 (In2CA) and 3¢ (3¢CA) with these anthropometric measures. We analyzed the data for 827 families of different sizes and configurations, which included 1520 premenopausal women. Nominally significant associations (Pp0.05) were found for a rare 3¢ variant allele (3¢CA-193) and BMI (P¼0.05), and for the more common 3¢CA-187 allele and weight (P¼0.04). These associations did not remain significant when adjusted for multiple comparisons. Haplotype analysis did not support an association between these variants and anthropometric measures. This study does not support an association between IGF1 and these anthropometric measures. Study limitations, including sample size and capturing genetic variation at IGF1 with these markers, could mean associations were missed.

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confidence: 92%

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confidence: 94%

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confidence: 97%

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Family-based association study of IGF1 microsatellites and height, weight, and body mass index

et al. 2010

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“…The most common allele contains 19 CA-repeats, which equals a length of 192-bp (28). In a previous study, we examined the role of the various lengths of the alleles of the IGF-I promoter polymorphism and observed an optimum for IGF-I levels and body height (29). Mean IGF-I levels and body height for homozygous carriers of the 192-bp allele, and homozygous carriers of the 194-bp-allele of this IGF-I gene promoter polymorphism were equal and significantly higher than the values measured in subjects homozygous for alleles smaller than 192-bp and longer than 194-bp, respectively, suggesting an optimum for IGF-I expression by these two variants.…”

Section: Genotyping Of the Igf-i Promoter Polymorphismmentioning

confidence: 99%

An insulin-like growth factor-I gene polymorphism modifies the risk of microalbuminuria in subjects with an abnormal glucose tolerance

Rietveld

Hofman²,

Pols³

et al. 2006

eur j endocrinol

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Objective: Microalbuminuria (MA) is related to cardiovascular disease both in diabetic patients and non-diabetic subjects. Design: We investigated whether a polymorphism near the promoter region of the IGF-I gene was related to the development of MA. Methods: For this study, 1069 participants of the Rotterdam study were selected (440 participants with an abnormal glucose tolerance (AGT), 220 participants with type 2 diabetes and 254 subjects with pre-diabetes, and 595 subjects with a normal glucose tolerance (NGT). Results: 787 subjects were carriers of the wild type IGF-I genotype (73.6%) and 282 subjects were variant carriers (26.4%) of this IGF-I gene polymorphism. Compared to subjects with NGT the risk for microalbuminuria was higher (Odds Ratio (OR): 3.1 (95% CI: 1.2-7.7); P ¼ 0.02) in variant carriers with AGT than in carriers of the wild type of this IGF-I gene polymorphism (OR: 2.2 (95% CI: 1.2 -4.0); P ¼ 0.009). Compared with wild type carriers with AGT, the relative risk for MA was unadjusted and non-significantly increased in variant carriers with AGT (1.6; 95% CI: 0.8 -2.9). However, after adjustment for possible confounding factors (age, gender, mean blood pressure, fasting insulin, fasting glucose and smoking) this risk became significant (OR: RR 2.1; 95% CI:1.1 -4.4; P ¼ 0.04). Conclusions: In subjects with AGT, a higher risk for MA was observed in variant carriers than in carriers of the wild type genotype of this IGF-I gene polymorphism. Since MA is primarily associated with cardiovascular disease in subjects with AGT, our study suggests that variant carriers have a higher risk for cardiovascular disease than carriers of the wild type when they develop an AGT. European Journal of Endocrinology 154 715-721

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“…The reaction was carried out in a final volume of 7.5 ml containing at least 5 ng of genomic DNA, 0.5 nmol/l forward primer (5 (32). IGF-I genotypes were determined as described previously (32).…”

Section: Determination Of Igf-i Genotypesmentioning

confidence: 99%

An IGF-I gene polymorphism modifies the risk of developing persistent microalbuminuria in type 1 diabetes

Hovind

Lamberts²,

Hop³

et al. 2007

eur j endocrinol

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Objective: Derangements of the GH-IGF-I axis have been associated with microalbuminuria (MA) in type 1 diabetes. The aim of this study was to investigate whether an IGF-I gene promoter polymorphism influenced the development of persistent MA in type 1 diabetes. Design: A prospective follow-up study of a cohort of 277 patients with newly diagnosed type 1 diabetes consecutively enrolled between September 1979 and August 1984. Methods: Urinary albumin excretion rate over 24 h was measured in each patient at least once a year. Persistent MA was defined as a urinary albumin excretion rate between 30 and 300 mg/24 h. Results: During a median follow-up of 18.0 years (range 1.0-21.5), 79 of 277 patients developed persistent MA. IGF-I gene genotype was available for 216 subjects; in 73% of the subjects, the wildtype genotype of this IGF-I gene polymorphism was present, while 27% had the variant type. At baseline, there were no differences in IGF-I levels and HbA 1c values between subjects with the wild type and subjects with variant type. By Kaplan-Meier analysis, subjects with the variant type of this polymorphism had during follow-up a higher risk of development of MA compared subjects with the wild type (PZ0.03). Conclusions: Subjects with the variant type of an IGF-I gene polymorphism had a significantly increased risk of developing MA. This risk was not mediated through changes in circulating IGF-I levels. Our study suggests that in type 1 diabetes, this IGF-I gene polymorphism is a risk factor of MA.European Journal of Endocrinology 156 83-90

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A polymorphic CA repeat in the IGF‐I gene is associated with gender‐specific differences in body height, but has no effect on the secular trend in body height

Cited by 77 publications

References 26 publications

Family-based association study of IGF1 microsatellites and height, weight, and body mass index

Family-based association study of IGF1 microsatellites and height, weight, and body mass index

An insulin-like growth factor-I gene polymorphism modifies the risk of microalbuminuria in subjects with an abnormal glucose tolerance

An IGF-I gene polymorphism modifies the risk of developing persistent microalbuminuria in type 1 diabetes

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