Association of common variants of TCF7L2 and PCSK2 with gestational diabetes mellitus in West Bengal, India

Abstract

The genetic etiology of gestational diabetes mellitus (GDM) was suggested to overlap with type-2 diabetes(T2D). Transcription factor 7-like 2 (TCF7L2) and Proprotein Convertase Subtilisin/Kexin type 2 (PCSK2) are T2D susceptibility genes of the insulin synthesis/processing pathway. We analyzed associations of TCF7L2 and PCSK2 variants with GDM risk and evaluated their potential impact on impaired insulin processing in an eastern Indian population. The study included 114 GDM (case) and 228 non-GDM pregnant women (control). rs7903146, rs4132670, rs12255372 of TCF7L2, and rs2269023 of PCSK2 were genotyped by PCR-RFLP, and genotype distributions were compared between case and control. Fasting serum proinsulin and C-peptide levels were measured by ELISA and the Proinsulin/C-peptide ratio was considered an indicator of proinsulin conversion. Significantly higher frequency of risk allele (T) of rs12255372 (p = 0.02, OR = 2.0, 95%CI = 1.11–3.64) and rs4132670 (p = 0.002, OR = 2.26, 95%CI = 1.32–3.87) of TCF7L2 was found in GDM cases than non-GDM controls; TT genotype was associated with significantly increased disease risk. In rs7903146 (TCF7L2) and rs2269023 (PCSK2), although the frequency of risk allele (T) was not significantly higher in cases than controls, an association of TT for both variants remained significant with higher GDM risk in the recessive model. Increased serum pro-insulin and proinsulin:c-peptide ratio was found in GDM than non-GDM women and the phenomenon showed significant association with careers of risk alleles for TCF7L2 variants. In conclusion, TCF7L2 and PCSK2 variants are related to GDM risk in the studied population and hence may serve as potential biomarkers for assessing the disease risk. TCF7L2 variants contribute to impaired insulin processing.

Keywords:

• Gestational diabetes mellitus
• genetic variants
• TCF7L2
• PCSK2
• proinsulin
• proinsulin:c-peptide ratio

Acknowledgments

We are thankful to the Hon’ble Vice Chancellor, Presidency University Kolkata, India.

Ethical approval

The study including its protocol was approved by the institutional ethics committee of the Institute of Postgraduate Medical Education and Research (IPGME&R), Kolkata, India. Memo No. Inst/IEC/2015/544B.Written informed consent was taken from each participant of this study before the collection of the sample.

Author contributions

J.B. did wet laboratory experimentation and analyzed the data. R.M. did statistical analyses. J.B. and C.D. drafted the manuscript. P.S., S.C., and D.M. supervised the diagnosis of GDM, collection of samples as well as participant’s details and critically reviewed the manuscript. A.G. conceived the study design, interpreted overall data, and prepared the final version of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

Financial support for this work was provided by the West Bengal State Govt. sponsored Presidency University FRPDF funds to Dr. Amlan Ghosh and by the Department of Biotechnology, Govt. of India, New Delhi, through DBT-BUILDER program, Presidency University, Kolkata.