Functional analysis of PCSK2 coding variants: A founder effect in the Old Order Amish population.

ABSTRACT:

Aims

In humans, noncoding variants of PCSK2, the gene encoding prohormone convertase 2 (PC2), have been previously associated with risk for and age of onset of type 2 diabetes (T2D). The aims of this study were to identify coding variants in PCSK2; to determine their possible association with glucose handling; and to determine functional outcomes for coding variants in biochemical studies.

Methods

Exome-wide genotyping was performed on 1725 Old Order Amish (OOA) subjects. PCSK2 coding variants were tested for association with diabetes-related phenotypes. In vitro analyses using transfected human PC2-encoding constructs were performed to determine the impact of each mutation on PC2 activity.

Results

We identified 10 rare missense coding variants in PCSK2 in various gen

SUBMITTER: Winters A 

PROVIDER: S-EPMC5572827 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature