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

Rietveld, Ingrid; Hofman, Albert; Pols, H A P; Duijn, C.M. van; Lamberts, S. W. J.; Janssen, Joseph A M J L

doi:10.1530/eje.1.02144

Cited by 12 publications

(12 citation statements)

References 38 publications

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“…Urine albumin and creatinine were determined by a turbidimetric method and measured by a Hitachi MODULAR P Analyzer (Roche/Hitachi Diagnostics, Mannheim, Germany). 28 Albumin-to-creatinine ratio (milligrams per gram) was estimated by dividing albumin by creatinine. Because albumin-to-creatinine ratio was not normally distributed, we used log-transformed values to obtain values per doubling of the albuminto-creatinine ratio.…”

Section: Kidney Functionmentioning

confidence: 99%

Kidney Function and Cerebral Blood Flow

Sedaghat¹,

Vernooij

Loehrer³

et al. 2016

Journal of the American Society of Nephrology

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CKD is linked with various brain disorders. Whereas brain integrity is dependent on cerebral perfusion, the association between kidney function and cerebral blood flow has yet to be determined. This study was performed in the framework of the population-based Rotterdam Study and included 2645 participants with mean age of 56.6 years (45% men). We used eGFR and albumin-to-creatinine ratio to assess kidney function and performed phase-contrast magnetic resonance imaging of basilar and carotid arteries to measure cerebral blood flow. Participants had an average (SD) eGFR of 86.3 (13.4) ml/min per 1.73 m 2 and a median (interquartile range) albumin-to-creatinine ratio of 3.4 (2.2-6.1) mg/g.In age-and sex-adjusted models, a higher albumin-to-creatinine ratio was associated with lower cerebral blood flow level (difference in cerebral blood flow [milliliters per minute per 100 ml] per doubling of the albumin-to-creatinine ratio, 20.31; 95% confidence interval, 20.58 to 20.03). The association was not present after adjustment for cardiovascular risk factors (P=0.10). Each 1 SD lower eGFR was associated with 0.42 ml/min per 100 ml lower cerebral blood flow (95% confidence interval, 0.01 to 0.83) adjusted for cardiovascular risk factors. Thus, in this population-based study, we observed that lower eGFR is independently associated with lower cerebral blood flow.

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Section: Kidney Functionmentioning

confidence: 99%

Kidney Function and Cerebral Blood Flow

Sedaghat¹,

Vernooij

Loehrer³

et al. 2016

Journal of the American Society of Nephrology

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“…Two cis-eQTL of IGF1 were found (rs10860862 and rs5742632) where the latter SNP is an intronic enhancer at a transcriptional factor binding site. IGF1 is a well-documented gene that plays a role in cardiovascular disorders [38], [39], [40], [41], [42] and metabolic disorders [43], [44], [45], [46], [47], [48], [49], [50], [51], [52]. IGF1 variants are associated with decreased body weight/size, abnormal glucose homeostasis, increased/decreased circulating insulin levels, decreased circulating IGF1 levels, and increased DBP/SBP values in mice [53], [54], [55].…”

Section: Resultsmentioning

confidence: 99%

Identification of IGF1, SLC4A4, WWOX, and SFMBT1 as Hypertension Susceptibility Genes in Han Chinese with a Genome-Wide Gene-Based Association Study

Yang

Chen

et al. 2012

PLoS ONE

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Hypertension is a complex disorder with high prevalence rates all over the world. We conducted the first genome-wide gene-based association scan for hypertension in a Han Chinese population. By analyzing genome-wide single-nucleotide-polymorphism data of 400 matched pairs of young-onset hypertensive patients and normotensive controls genotyped with the Illumina HumanHap550-Duo BeadChip, 100 susceptibility genes for hypertension were identified and also validated with permutation tests. Seventeen of the 100 genes exhibited differential allelic and expression distributions between patient and control groups. These genes provided a good molecular signature for classifying hypertensive patients and normotensive controls. Among the 17 genes, IGF1, SLC4A4, WWOX, and SFMBT1 were not only identified by our gene-based association scan and gene expression analysis but were also replicated by a gene-based association analysis of the Hong Kong Hypertension Study. Moreover, cis-acting expression quantitative trait loci associated with the differentially expressed genes were found and linked to hypertension. IGF1, which encodes insulin-like growth factor 1, is associated with cardiovascular disorders, metabolic syndrome, decreased body weight/size, and changes of insulin levels in mice. SLC4A4, which encodes the electrogenic sodium bicarbonate cotransporter 1, is associated with decreased body weight/size and abnormal ion homeostasis in mice. WWOX, which encodes the WW domain-containing protein, is related to hypoglycemia and hyperphosphatemia. SFMBT1, which encodes the scm-like with four MBT domains protein 1, is a novel hypertension gene. GRB14, TMEM56 and KIAA1797 exhibited highly significant differential allelic and expressed distributions between hypertensive patients and normotensive controls. GRB14 was also found relevant to blood pressure in a previous genetic association study in East Asian populations. TMEM56 and KIAA1797 may be specific to Taiwanese populations, because they were not validated by the two replication studies. Identification of these genes enriches the collection of hypertension susceptibility genes, thereby shedding light on the etiology of hypertension in Han Chinese populations.

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“…Over the past decade, several studies have demonstrated associations of the promoter region of the IGF-I gene with the human cardiovascular system and also with the metabolic phenotype and growth in childhood and adults (9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)25). An increased risk of mortality was found in patients after myocardial infarction, in those who were variant carriers of the IGF-I polymorphism (19).…”

Section: Discussionmentioning

confidence: 99%

“…Thus, several studies showed associations between a common IGF-I promoter region polymorphism and low circulating IGF-I levels, and subsequently the development of cardiovascular disease in adulthood (13,14,(16)(17)(18)(19). We hypothesized that this IGF-I promoter region polymorphism already influences the development of blood pressure and left heart dimensions in early childhood.…”

Section: Introductionmentioning

confidence: 97%

“…This variant has also been demonstrated to be associated with cardiovascular disease, type 2 diabetes and variation in growth characteristics, including birth size and final height in adulthood, in the normal population (9)(10)(11)(12)(13)(14)(15). It was also suggested that non-carriage of the 192/194 bp alleles was associated with cardiovascular disease (16)(17)(18)(19).…”

Section: Introductionmentioning

confidence: 98%

See 1 more Smart Citation

A variant of the IGF-I gene is associated with blood pressure but not with left heart dimensions at the age of 2 years: the Generation R Study

Houten

Mook‐Kanamori

Osch-Gevers

et al. 2008

European Journal of Endocrinology

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Background and objective: A common variant of the IGF-I gene has been shown to be associated with cardiovascular disease in adulthood. The objective of this study was to examine whether this variant of the IGF-I gene is associated with blood pressure and left heart dimensions in early childhood. Research design and methods: This study was embedded in the Generation R Study, a population-based prospective cohort study from foetal life onwards. IGF-I promoter region was genotyped in DNA obtained from cord blood. Blood pressure (systolic and diastolic) and echocardiography (left ventricular mass, left atrial diameter and aortic root diameter) measurements were performed at the age of 2 years. Analyses were performed in 538 subjects. Results: Eight alleles of the IGF-I promoter region were identified. In total, 43% of the subjects were homozygous for the 192 bp allele (wild type), 46% were heterozygous and 11% were non-carriers. Significantly lower systolic and diastolic blood pressures were found in non-carrier subjects (difference compared with homozygous subjects: K4.4 (95% confidence interval (CI) K7.8 to K1.1) mmHg and K3.5 (95% CI: K6.9 to K0.1) mm respectively). No significant differences were found for left heart dimensions at the age of 2 years. No association was found when we used a previously proposed alternative classification of the IGF-I gene. Conclusion:The variant type of the IGF-I promoter region is associated with lower blood pressure but not with left heart dimensions at the age of 2 years. Follow-up studies are needed to examine whether these differences persist in later life.

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

Cited by 12 publications

References 38 publications

Kidney Function and Cerebral Blood Flow

Kidney Function and Cerebral Blood Flow

Identification of IGF1, SLC4A4, WWOX, and SFMBT1 as Hypertension Susceptibility Genes in Han Chinese with a Genome-Wide Gene-Based Association Study

A variant of the IGF-I gene is associated with blood pressure but not with left heart dimensions at the age of 2 years: the Generation R Study

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