Effects of variation in retinol binding protein 4 gene and adipose specific expression of gestational diabetes in Beijing, China

doi:10.1016/j.diabres.2012.02.017

Diabetes Research and Clinical Practice

Volume 97, Issue 2, August 2012, Pages 283-289

https://doi.org/10.1016/j.diabres.2012.02.017 Get rights and content

Abstract

Objective

To investigate the clinical features of GDM in China and the effects of RBP4 genetic variants, and also to identify RBP4 expression changes in mRNA and protein levels.

Research design and methods

1595 Chinese pregnant women were included in this study. Four known RBP4 single nucleotide polymorphisms (SNPs) were genotyped in 505 cases and 687 controls. Expression levels of adipose specific RBP4 mRNA and protein were detected in 41 samples of subcutaneous adipose tissue.

Results

The estimated indices of insulin resistance were gradually increased from NGT, GIGT to GDM. Two single SNPs were associated with GDM (rs3758539 G vs A, OR = 1.446, P = 0.009; rs3758539 GG vs AG + AA, OR = 1.532, P = 0.006; rs12265684 C vs G, OR = 1.296, P = 0.038) and a haplotype of 3 common SNPs [G-G-T] was increased in subjects with GDM and GIGT (OR = 1.322, 95% CI 1.054–1.659, P = 0.016). RBP4 mRNA expression in adipose tissue of GDM patients was significantly increased in comparison to control subjects (1.438 ± 0.187 vs 1.034 ± 0.062, p = 0.025).

Conclusion

This finding suggests that impaired insulin sensitivity has an early onset in mild gestational intolerance. Two single SNPs were associated with GDM in the case-control study while a haplotype of 3 common SNPs [G-G-T] was increased in glucose intolerance subjects.

Section snippets

Subjects

Study subjects were collected from the outpatient clinic of Peking Union Medical College Hospital (PUMCH) from September 2005 to March 2008. All subjects were of Han Chinese and lived in the same region (Beijing, China) at the time of the study. Briefly, all pregnant women in outpatient were subjected to a standardized 50 g glucose challenge test (GCT) at a time period from the 24 to 28th gestational week. Patients with pregestational diabetes mellitus, treatment with steroid hormones, serious

The anthropometric and biochemical features of study population

A total of 1596 subjects were included in the study. Baseline characteristics show that age, prepregnancy BMI and blood pressure were significantly increased in GCT+ compared to GCT− subjects. Within the GCT positive cohort, GDM subjects were significantly older, had higher BMI and blood pressure and more often reported of a positive family history of diabetes (Table 1). Furthermore, WBC, TG, hsCRP and insulin level during OGTT were significantly increased in GDM in comparison to GIGT or NGT.

Discussion

A true increase in the prevalence of GDM, aside from its adverse consequences for infants in the newborn period, might also reflect or contribute to the current patterns of increasing diabetes and obesity [6]. According to our study, insulin sensitivity decreases in both GDM and GIGT while beta cell function were significantly decreased when evaluated by indices calculated from both fasting and postprandial glucose and insulin level during OGTT. This finding suggests that impaired insulin

Conflict of interest

The authors declare that they have no conflict of interest.

Acknowledgments

We sincerely appreciate all participants in this study and all medical staffs for their invaluable assistance in providing and collecting specimen. We thank Shanghai BioWing Applied Biotechnology Co. Ltd. for providing genotyping service. This work was supported by grants from the Project of Capital Medical Development and Research, Beijing, PR China (no. 2002-1017).

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View all citing articles on Scopus

^☆: Part of the study has been presented at the 14th ICE meetings, Tokyo, May, 27th, 2010.

View full text

Effects of variation in retinol binding protein 4 gene and adipose specific expression of gestational diabetes in Beijing, China☆

Abstract

Objective

Research design and methods

Results

Conclusion

Section snippets

Subjects

The anthropometric and biochemical features of study population

Discussion

Conflict of interest

Acknowledgments

Eur J Obstet Gynecol Reprod Biol

Am J Hum Genet

Mol Genet Metab

Cell Metab

J Lipid Res

Race/ethnicity and other risk factors for gestational diabetes

Am J Epidemiol

Ethnic differences in perinatal outcome of gestational diabetes mellitus

Diabetes Care

Why does ethnicity affect prevalence of gestational diabetes? The underwater volcano theory

Diabet Med

Increasing prevalence of gestational diabetes mellitus: a public health perspective

Diabetes Care

Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes

Nature

RBP4, an unexpected adipokine

Nat Med

Retinol-binding protein 4 and insulin resistance in lean, obese, and diabetic subjects

N Engl J Med

A genome-wide scan for loci linked to plasma levels of glucose and HbA(1c) in a community-based sample of Caucasian pedigrees: The Framingham Offspring Study

Diabetes

Identification of a regulatory SNP in the retinol binding protein 4 gene associated with type 2 diabetes in Mongolia

Hum Genet

Effects of genetic variation in the human retinol binding protein-4 gene (RBP4) on insulin resistance and fat depot-specific mRNA expression

Diabetes

Effect of RBP4 gene variants on circulating RBP4 concentration and type 2 diabetes in a Chinese population

Diabet Med

Development and preliminary application of enzyme-linked immunosorbent assay for human net insulin in serum

Chin J Endocrinol Metab