Novel association between a transient receptor potential cation channel subfamily M member 5 expression quantitative trait locus rs35197079 and decreased susceptibility of gestational diabetes mellitus in a Chinese population

Abstract

Aims/Introduction Emerging evidence suggests that expression quantitative trait loci (eQTLs) are more likely to associate with complex diseases. Transient receptor potential cation channel subfamily M member 5 (TRPM5) is a ubiquitously expressed voltage‐gated cation channel that acts indispensably to trigger insulin secretion in pancreatic β‐cells. The present study evaluated the association between TRPM5 eQTL single‐nucleotide polymorphisms and the risk of gestational diabetes mellitus (GDM) in a Chinese population. Materials and Methods A total of 380 unrelated Chinese pregnant women including 241 GDM patients and 139 controls were included in this study. The eQTL single‐nucleotide polymorphisms of TRPM5 were obtained from the GTEx eQTL Browser, and were subsequently genotyped using the Agena MassARRAY iPLEX platform. Results Logistic regression analysis and linear regression analysis showed that rs35197079 and rs74848824 were significantly associated with reduced GDM risk and lower fasting plasma glucose levels after adjusting confounder factors in dominant genetic models. Stratification analysis based on pre‐pregnancy body mass index validated a strong association between rs35197079 and GDM susceptibility in underweight and normal weight individuals. Luciferase and electrophoretic mobility shift assays carried out in rat pancreatic β‐cells showed that rs35197079 was functional. Conclusions The TRPM5 eQTL single‐nucleotide polymorphism rs35197079 was associated with decreased GDM susceptibility in a Chinese population, especially in underweight and normal weight pregnant women, and it was functional in modulating gene transcription.

Taste perception genomics in gestational diabetes mellitus: A systematic review

“…7 Furthermore, SNPs at TRPM5 inhibit the expression of TRPM5, which leads to impaired sweet, salt and bitter taste stimuli perception and decreases aversion to high sweet and salt consumption. 8 This suggests that the TRPM5 SNP variant C and A alleles, which were higher in the GDM group, are significantly associated with increased risk of GDM and might also be associated with impaired sweet, salt and bitter perception. Studies also reported that activation of TRPM5 in pancreatic beta cells is responsible for the taste transduction and regulates glucose homeostasis by glucose-induced insulin secretion.…”

“…SNP CC genotype (rs74848824) were significantly associated with increased risk of GDM. 7,8 Studies reported that the TAS2R9 rs3741845 C allele decreases the bitter taste stimuli threshold in pregnant women with GDM and leads to increased bitter taste stimuli perception. 7 Furthermore, SNPs at TRPM5 inhibit the expression of TRPM5, which leads to impaired sweet, salt and bitter taste stimuli perception and decreases aversion to high sweet and salt consumption.…”

“…Overall, five studies investigated variation of taste perception and preferences among pregnant women with GDM and NGT [3][4][5][6][7][8] (Table 1). Tepper et al 3 and Belzer et al 4 showed that pregnant women with GDM had a greater preference for sweetness, creaminess and overall flavour in response to a test meal (sucrose-sweetened milk drink) than pregnant women with NGT.…”

“…receptor genes such as the TAS1R2, TAS2R7, TAS2R9, CD36, SLC2A2 and TRPM5 genes. 7,8 The studies reported that the TAS2R9 SNP C allele (rs3741845), TRPM5 SNP AA genotype (rs35197079) and TRPM5 SNP CC genotype (rs74848824) were significantly associated with increased risk of GDM 7,8 (Supplementary Table 2).…”

“…2,3,5,6 Although altered taste perception is common during pregnancy, several studies have reported that alterations in the perception of sweet, salty and fat tastes are associated with increased GDM susceptibility. [3][4][5][6][7][8] Genetic studies have reported that polymorphisms in genes encoding taste receptors, such as the TAS1Rs gene (sweet, sour and umami taste), TAS2Rs gene (bitter and sweet taste), TRPV1 gene (salt taste), CD36 gene (fat taste), TRPM5 gene (bitter, sweet, umami tastes and glucose homeostasis) and others such as the SLC2A2 gene (glucose transporter type 2 facilitated insulin secretion), might lead to altered taste perception and constitute a non-modifiable risk factor for GDM susceptibility. 7,8 The main objective of this study was to review variation in taste preferences and genetic polymorphisms in the loci encoding taste receptors among pregnant women with GDM (Figure 1).…”