Islet RNA was isolated from hand-picked islets as described (39), using the Arcturus PicoPure RNA Isolation Kit (Applied Biosystems, Foster City, CA), according to the procedure recommended by the manufacturer for RNA extraction from cell pellets and was accordingly treated with DNase to remove the contamination with genomic DNA. Reverse transcription to cDNA was performed using a High Capacity cDNA Reverse Transcription Kit (Themofisher). The rs4502156 and rs7163757 SNPs were genotyped by qPCR using a commercial TaqMan assay (Applied Biosystems). VPS13C, C2CD4A, and C2CD4B mRNA abundances were measured relative to ACTB in corresponding RNA samples by qRT-PCR using commercial TaqMan assays (Applied Biosystems) and the ΔCT method. As a quality control step, samples with ΔCT standard deviation > 0.2 were excluded from the analysis. The association between VPS13C expression and genotype was tested using an ANCOVA model, controlling for age, sex, and BMI and implemented in R (52). The association of genotype with C2CD4A and C2CD4B was analyzed in the same manner. Linkage disequilibrium (LD) values for SNPs in the Tuscan population used here were obtained at: http://www.1000genomes.org/faq/which-populations-are-part-your-study.