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Sequence variation in IGF1R is associated with differences in insulin levels in nondiabetic Old Order Amish.

ABSTRACT: BACKGROUND:Insulin growth factor-1 receptor (IGF1R) encodes the insulin-like growth factor 1 receptor, a transmembrane tyrosine kinase receptor located on chromosome 15q26.3, in a region of linkage (LOD = 2.53, P = 0.00032) to Insulin30 on an OGTT in the Old Order Amish. Mouse models with beta-cell-specific deficiency of IGF1R demonstrate defects in glucose-stimulated insulin secretion. METHODS:To test the hypothesis that genetic variation in IGF1R is associated with impaired insulin secretion, we genotyped 54 SNPs in 778 nondiabetic subjects from the AFDS who had undergone OGTTs and tested them for association with ln Insulin30 and ISI. RESULTS:No individual SNPs were significantly associated with ln Insulin30 or ISI using a multiple hypothesis testing adjusted P < 0.002. Tests of association of 4-SNP haplotypes constructed by a windowing approach revealed an association of the CTTG-variant of a 4-SNP haplotype found in intron 20 (rs1784195-rs2715439-rs8034284-rs12440962) with lower ISI levels (beta = 0.18, SE(beta) = 0.05, P = 0.001). CONCLUSIONS:Sequence variation in IGF1R may influence insulin secretory function, although further studies in other populations will be needed to confirm these findings.

SUBMITTER: Naj AC

PROVIDER: S-EPMC2837841 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature

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Sequence variation in IGF1R is associated with differences in insulin levels in nondiabetic Old Order Amish.

Naj Adam C AC Kao Wen-Hong L WH O'Connell Jeffrey R JR Mitchell Braxton D BD Silver Kristi D KD

Diabetes/metabolism research and reviews 20091101 8

<h4>Background</h4>Insulin growth factor-1 receptor (IGF1R) encodes the insulin-like growth factor 1 receptor, a transmembrane tyrosine kinase receptor located on chromosome 15q26.3, in a region of linkage (LOD = 2.53, P = 0.00032) to Insulin30 on an OGTT in the Old Order Amish. Mouse models with beta-cell-specific deficiency of IGF1R demonstrate defects in glucose-stimulated insulin secretion.<h4>Methods</h4>To test the hypothesis that genetic variation in IGF1R is associated with impaired insu ...[more]

PMID: 19877134

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Project description:Complementary and alternative medicine (CAM) in the form of vitamin and supplement use is increasingly prevalent in the United States. The interplay between CAM use and use of conventional medications is not well studied. We examined this issue in Old Order Amish (OOA), a population lacking several factors known to influence supplement use, whose culture and barriers to conventional medications may result in high rates of supplement use.We characterized the patterns of supplement use in OOA, including the extent to which CAM use aggregates in families, and assessed whether higher use of supplements is associated with lower medication use.We conducted a cross-sectional study of conventional medications and supplements in 2,372 adult Amish from the Lancaster County, PA, area. Data were collected through face-to-face interviews. Supplements were subcategorized as herbal vs vitamin/mineral supplements.Seventy-seven percent of all Amish adults reported current supplement use, whereas 22% reported medication use. Women used supplements more often and used more supplements than men, and familial aggregation of supplement use was stronger in family pairs involving women. Supplement use was associated with less medication use after controlling for age, sex, body mass index, and self-reported histories of hypertension, diabetes, and hyperlipidemia (adjusted odds ratio [OR] 0.96, 95% CI 0.92 to 1.00; P=0.047). This association was driven primarily by use of herbal supplements (adjusted OR 0.94, 95% CI 0.89 to 0.99; P=0.025) as vitamin/mineral supplements were not associated with different use of medication (adjusted OR 0.99, 95% CI 0.90 to 1.09; P=0.8). In analyses limited to cardiovascular medications and cardiovascular supplements in participants with hyperlipidemia, hypertension, or diabetes, supplement use was not associated with conventional medication use.OAA, particularly women, take dietary supplements much more frequently than they use conventional medications. Use of herbal supplements is associated with less use of conventional medications, whereas vitamin/mineral supplement use is not.

Dataset Information

Sequence variation in IGF1R is associated with differences in insulin levels in nondiabetic Old Order Amish.

Publications

Sequence variation in IGF1R is associated with differences in insulin levels in nondiabetic Old Order Amish.

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