Abstract
Phosphatidylinositol-specific phospholipase C X domain 3 (PLCXD3) has been shown to influence pancreatic β-cell function by disrupting insulin signaling. Herein, we investigated two genetic variants in the PLCXD3 gene in relation to type 2 diabetes (T2D) or metabolic syndrome (MetS) in the Emirati population. In total, 556 adult Emirati individuals (306 T2D and 256 controls) were genotyped for two PLCXD3 variants (rs319013 and rs9292806) using TaqMan genotyping assays. The frequency distribution of minor homozygous CC genotype of rs9292806 and GG genotype of rs319013 were significantly higher in subjects with MetS compared to Non-MetS (p < 0.01). The minor homozygous rs9292806-CC and rs319013-GG genotypes were significantly associated with increased risk of MetS (adj. OR 2.92; 95% CI 1.61–5.3; p < 0.001) (adj. OR 2.62; 95% CI 1.42–4.83; p = 0.002), respectively. However, no associations were detected with T2D. In healthy participants, the homozygous minor genotypes of both rs9292806 and rs319013 were significantly higher fasting glucose (adj. p < 0.005), HbA1c (adj. p < 0.005) and lower HDL-cholesterol (adj. p < 0.05) levels. Data from T2D Knowledge Portal database disclosed a nominal association of rs319013 and rs9292806 with T2D and components of MetS. Bioinformatics prediction analysis showed a deleterious effect of rs9292806 on the regulatory regions of PLCXD3. In conclusion, this study identifies rs319013 and rs9292806 variants of PLCXD3 as additional risk factors for MetS in the Emirati population.
Highlights
Metabolic syndrome (MetS) is a major health problem, referring to cluster risk factors that include obesity, dyslipidemia, hyperglycemia and hypertension [1,2,3]
Further investigations revealed that phospholipase C X domain 3 (PLCXD3) is involved in insulin signaling and glucose sensing, suggesting that PLCXD3 might be regarded as a candidate gene for pre-diabetes and metabolic syndrome
The first cohort consisted of participants from United Arab Emirates (UAE) national diabetes and lifestyle study (UAEDIAB) that includes participants living in Dubai, Sharjah, and the Northern Emirates collected from door to door visits as described previously [12,13,14]
Summary
Metabolic syndrome (MetS) is a major health problem, referring to cluster risk factors that include obesity, dyslipidemia, hyperglycemia and hypertension [1,2,3]. The International Diabetes Federation (IDF) estimates that a quarter of the adult population worldwide suffers from MetS [1]. Further investigations revealed that PLCXD3 is involved in insulin signaling and glucose sensing, suggesting that PLCXD3 might be regarded as a candidate gene for pre-diabetes and metabolic syndrome. Despite the role of PLCXD3 in β-cell function, until now no studies have linked genetic variants in the PLCXD3 gene with T2D, MetS or its related traits. The present study aims to investigate the association of two intronic SNPs “rs319013 and rs9292806” with T2D or MetS in the Emirati population
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