Novel and known variants in PCSK1 – Functional characterization and clinical associations with obesity in children

PCSK1 is a physiologic candidate gene for obesity with support from rare monogenic cases and recent association studies. We aimed to screen the gene for novel variants, to assess their effects on obesity and to evaluate their functional relevance in vitro. We sequenced the coding region and 5′UTR in 52 obese children selected for high proinsulin and early impaired glucose tolerance. We identified 8 known SNPs and 2 novel heterozygous variants: a splice site mutation and a missense mutation S24C. To evaluate the clinical relevance, we genotyped the SNPs in 718 obese and 977 lean children. rs6232 was significantly…