A nonsense p.Arg684Ter variant in the
TBC1D4 gene has been identified in the
Greenlandic Inuit population that is associated with increased risk of
type II diabetes. The variant mainly affects individuals with two copies of the mutation, indicating
recessive inheritance. Although the mutation does not effect the short isoform of the protein, it introduces a premature stop codon in the long isoform, resulting in the absence of the long isoform protein in muscle tissue.
Homozygous carriers of the p.Arg684Ter allele have lower concentrations of fasting plasma glucose and insulin. They also have a markedly increased risk of
Type II Diabetes — individuals with two mutant genes have about 10 times the chance of contracting Type II diabetes (
odds ratio = 10.3) compared to noncarriers. Approximately 3.8% of Greenlanders are homozygous for the mutation, which is estimated to be responsible for approximately 10% of Type II Diabetes cases in Greenland. == References ==