Endocrine DOI 10.1007/s12020-016-1058-7 ORIGINAL ARTICLE Polymorphism of the renalase gene in gestational diabetes mellitus Syeda Sadia Fatima 1 ● Zehra Jamil 1 ● Faiza Alam 1 ● Hajira Zafar Malik 2 ● Sarosh Irfan Madhani 2 ● Muhammad Saad Ahmad 2 ● Tayyab Shabbir 2 ● Muhammed Noman Rehmani 2 ● Amna Rabbani 2 Received: 18 April 2016 / Accepted: 11 July 2016 © Springer Science+Business Media New York 2016 Abstract Renalase is considered as a novel candidate gene for type 2 diabetes. In this study, we aimed to investigate the relationship of serum renalase and two single nucleotide polymorphisms with gestational diabetes mellitus. One hundred and ninety-eight normotensive pregnant females (n = 99 gestational diabetes mellitus; n = 99 euglycemic pregnant controls) were classified according to the Inter- national Association of the Diabetes and Pregnancy Study criteria. Fasting and 2-h post glucose load blood levels and anthropometric assessment was performed. Serum renalase was measured using enzyme-linked immunosorbent assay, whereas DNA samples were genotyped for renalase single nucleotide polymorphisms rs2576178 and rs10887800 using Polymerase chain reaction-Restriction fragment length polymorphism method. In an age-matched case control study, no difference was observed in the serum levels of renalase (p > 0.05). The variant rs10887800 showed an association with gestational diabetes mellitus and remained significant after multiple adjustments (p < 0.05), whereas rs2576178 showed weak association (p = 0.030) that was lost after multiple adjustments (p = 0.09). We inferred a modest association of the rs10887800 polymorphism with gestational diabetes. Although gestational diabetes mellitus is self-reversible, yet presence of this minor G allele might predispose to metabolic syndrome phenotypes in near the future. Keywords Gestational diabetes ● Renalase ● Metabolic syndrome ● BMI ● Obesity Introduction Gestational diabetes mellitus (GDM) affects 15 % pregnant women worldwide [1], whereas its prevalence is estimated to be 8 % in Pakistan [2]. The altered blood glucose during pregnancy may lead to decreased insulin sensitivity, enabling the pathogenesis of GDM [3] and eventually the raised blood glucose level causing an unwarranted effect on both the mother and developing fetus [4]. It also increases the risk of developing type 2 diabetes mellitus (T2DM) in the near future [5, 6]. Women with higher pre-pregnancy body mass index (BMI ≥ 25 kg/m 2 ) are at an increased risk for developing metabolic complications during pregnancy such as GDM. Increased or hypertrophied adipose tissue leads to exacer- bated release of adipo-cytokine in the circulation, which in turn activates various inflammatory mechanisms within the body. The effect of these adipo-cytokines leads to insulin resistance [7, 8]. It is well established that fatty acids released from adipocytes compete with the glucose uptake by cells and impair insulin signaling via kinases activity [9]. Thus, increased adiposity [expressed in body fat % (BF%)] may be considered as a common risk factor for insulin resistance in both T2DM and GDM [10, 11]. * Syeda Sadia Fatima sadia.fatima@aku.edu 1 Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan 2 Medical College, Aga Khan University, Karachi, Pakistan Electronic supplementary material The online version of this article (doi:10.1007/s12020-016-1058-7) contains supplementary material, which is available to authorized users. Zehra Jamil and Faiza Alam have contributed equally to this work. Hajira Zafar Malik, Sarosh Madhani, Noman Rehmani, Muhammad Saad Ahmad, Amna Rabbani, and Tayyab Shabbir have contributed equally to this work.