Common genetic variants in ADCY5 and gestational glycemic traits

Abstract

Two meta-analysis of genome wide association studies identified two variants at adenylate cyclase 5 (ADCY5) associated with type 2 diabetes mellitus, fasting and 2-hour glucose in non-pregnant individuals of European descent. The objective of our study was to explore the role of common variants in ADCY5 on gestational glycemic traits, including plasma glucose, insulin values, β cell function and insulin resistance in the fasted state as well as plasma glucose 1 hour after a 50-gram glucose challenge test among Chinese Han women. Homoeostasis model assessment (HOMA) was used to quantify β cell function (HOMA1-β and HOMA2-β) and insulin resistance (HOMA1-IR and HOMA2-IR). Thirty-five single nucleotide polymorphisms (SNPs) in ADCY5 were genotyped in 929 unrelated Chinese Han women with singleton pregnancies. Three SNPs (rs6797915, rs9856662 and rs9875803) displayed evidence for association with plasma glucose 1 hour after a 50-gram glucose challenge test (P = 0.042, 0.018 and 0.018, respectively), one (rs6777397) displayed evidence for association with HOMA1-β (P = 0.014), and one (rs6762009) displayed evidence for association with HOMA1-IR (P = 0.033). These results provide additional insight into the effects of genetic variation within ADCY5 in glucose metabolism, especially during pregnancy and in non-European descent populations. OPEN ACCESS Citation: Lin R, Yuan Z, Zhang C, Ju H, Sun Y, Huang N, et al. (2020) Common genetic variants in ADCY5 and gestational glycemic traits. PLoS ONE 15(3): e0230032. https://doi.org/10.

Identifying novel genetic loci associated with polycystic ovary syndrome based on its shared genetic architecture with type 2 diabetes

“…rs4234212 is an eQTL for both ADCY5 and SEC22A. ADCY5 encodes membrane-bound adenylyl cyclase enzyme-5 that converts adenosine triphosphate to the cyclic adenosine monophosphate and pyrophosphate and regulates glucose-induced insulin secretion ( Lin et al, 2020 ). Horikoshi et al (2013 ) reported that variants in ADCY5 were associated with lower birth weight in the European population, implying that ADCY5 may be linked to a poor maternal–fetal environment.…”

Effects of Whole-Body Adenylyl Cyclase 5 (Adcy5) Deficiency on Systemic Insulin Sensitivity and Adipose Tissue

“…Individual variation in Adcy5 interaction with the genetic background may also explain the heterogeneous findings from genome-wide association studies and candidate gene approaches reporting different directions of the associations of ADCY5 genetic variants with obesity, diabetes-related quantitative traits and the risk of type 2 diabetes [ 1 , 2 , 5 , 8 , 9 ].…”

“…In addition, ADCY5 genetic variants have been associated with lower birth weight [ 3 ], gestational diabetes [ 4 ], and parameters of insulin sensitivity in children with obesity [ 5 ]. However, associations between the ADCY5 genotype are heterogeneous and range from being protective against T2D [ 1 , 6 , 7 ] to increasing the diabetes risk [ 1 , 2 , 5 , 8 , 9 ]. In three cases of exceptional inherited longevity, exome sequencing revealed ADCY5 as candidate gene [ 10 ].…”

Identification of hub genes and functional modules in colon adenocarcinoma based on public databases by bioinformatics analysis

“…It may be the most abundant member of the ADCY family in human islets (30). Current studies have mainly focused on movement disorders related to ADCY5 mutation (31,32), but other research has also reported that the genetic variation of ADCY5 affects glucose metabolism, leading to the occurrence of type 2 diabetes (33). Although no previous studies have reported a correlation between ADCY5 and CRC, several bioinformatic analyses suggest that ADCY5 is a hub gene of CRC and have designated it as a potential biomarker of CRC (34).…”