The vitamin D receptor polymorphism in the translation initiation codon is a risk factor for insulin resistance in glucose tolerant CaucasiansReport as inadecuate




The vitamin D receptor polymorphism in the translation initiation codon is a risk factor for insulin resistance in glucose tolerant Caucasians - Download this document for free, or read online. Document in PDF available to download.

BMC Medical Genetics

, 2:2

First Online: 15 February 2001Received: 06 January 2001Accepted: 15 February 2001

Abstract

BackgroundAlthough vitamin D receptor VDR polymorphisms have been shown to be associated with abnormal glucose metabolism, the reported polymorphisms are unlikely to have any biological consequences. The VDR gene has two potential translation initiation sites. A T-to-C polymorphism has been noted in the first ATG f allele, abolishing the first translation initiation site and resulting in a peptide lacking the first three amino acids F allele. We examined the role of this polymorphism in insulin sensitivity and beta cell function. This study included 49 healthy Caucasian subjects 28 females, age 28 ± 1 years old, body mass index 24.57 ± 0.57 kg-m, waist-hip ratio 0.81 ± 0.01 cm-cm. They were all normotensive less than 140-90 mmHg and glucose tolerant, which was determined by a standard 75-gm oral glucose tolerance test. Their beta cell function %B and insulin sensitivity %S were calculated based on the Homeostasis Model Assessment HOMA. Their genotypes were determined by a polymerase chain reaction-restriction fragment length polymorphism analysis. Phenotypes were compared between genotypic groups.

ResultsThere were 18 FF, 21 Ff, and 10 ff subjects. Since only 10 ff subjects were identified, they were pooled with the Ff subjects during analyses. The FF and Ff-ff groups had similar glucose levels at each time point before and after a glucose challenge. The Ff-ff group had higher insulin levels than the FF group at fasting P=0.006, 30 minutes P=0.009, 60 minutes P=0.049, and 90 minutes P=0.042. Furthermore, the Ff-ff group also had a larger insulin area under the curve than the FF group P=0.009. While no difference was noted in %B, the Ff-ff group had a lower %S than the FF group 0.53 vs. 0.78, P=0.006. A stepwise regression analysis confirmed that the Fok I polymorphism was an independent determinant for %S, accounting for 29.3% of variation in %S when combined with waist-hip ratio.

ConclusionsWe report that the Fok I polymorphism at the VDR gene locus is associated with insulin sensitivity, but has no influence on beta cell function in healthy Caucasians. Although this polymorphism has been shown to affect the activation of vitamin D-dependent transcription, the molecular basis of the association between this polymorphism and insulin resistance remains to be determined.

AbbreviationsHOMAHomeostasis Model Assessment

VDRvitamin D receptor

BMDbone mineral density

PCRpolymerase chain reaction.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2350-2-2 contains supplementary material, which is available to authorized users.

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Author: Ken C Chiu - Lee-Ming Chuang - Carol Yoon

Source: https://link.springer.com/







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