In a study of pharmacogenomic variants, researchers found a novel and biologically plausible polymorphism associated with differences in HbA1c levels during metformin monotherapy in African American patients with type 2 diabetes (T2D). “These results highlight the importance of diversity in pharmacogenomic studies,” the authors conclude.
The Diabetes Multi-omic Investigation of Drug Response (DIAMOND) cohort study included patients with T2D in a southeastern Michigan health system who had available genome-wide genotype data and longitudinal electronic records of laboratory results and medication fills. Results were assessed for replication in an independent cohort of African American participants from Kaiser Permanente Northern California (KPNC) and in European American participants from DIAMOND.
“The discovery set consisted of 447 African American participants, whereas the replication sets included 353 African American KPNC participants and 466 European American DIAMOND participants,” write the authors. “The primary analysis identified a variant, rs143276236, in the gene ARFGEF3, which met the threshold for genome-wide significance, replicated in KPNC African Americans, and was still significant in the meta-analysis (P = 1.17 × 10−9). None of the significant discovery variants replicated in European Americans DIAMOND participants.”