Our study revealed an unexpected role of ZnT8 in regulating peripheral 5-HT biogenesis and intestinal microenvironment, which might contribute to the increased risk of obesity and type 2 diabetes.
Most notably, 5 SNPs from 5 genes [body mass index (BMI), hip circumference: rs3751812/FTO; fasting plasma glucose, hemoglobin A1c: rs4607517/GCK; very-low-density lipoprotein: rs10830963/MTNR1B; BMI: rs13266634/SLC30A8, and total cholesterol, low-density lipoprotein: rs7578597/THADA] were significantly associated with obesity, glycemic, and lipid phenotypes when using the multiple testing significance threshold of 0.0015.
In the present study, we examined the association between variants in fat mass- and obesity-associated [rs9939609 (A/T)], melanocortin 4 receptor [rs17782313 (C/T), and rs12970134 (A/G)], SLC30A8 [rs13266634 (C/T)], and a member of the potassium voltage-gated channels [rs2237892(C/T)] genes in diabetes patients from Saudi Arabia.
Analysis of the current list of type 2 diabetes susceptibility variants revealed nominal evidence for effect size heterogeneity for the SLC30A8 locus alone (RR(obese) 1.08 [1.01-1.15]; RR(nonobese) 1.18 [1.10-1.27]: P(DIFF) = 0.04).