title: Role of a proline insertion in the insulin promoter factor 1 (IPF1) gene in African Americans with type 2 diabetes.
abstract: African Americans have twice the prevalence of type 2 diabetes as Caucasians and much greater genetic diversity. We identified an inframe insertion of a proline in the insulin promoter factor 1 (IPF1) gene (InsCCG243), which was relatively common (minor allele frequency approximately 0.08) in African Americans and showed a trend to association with type 2 diabetes in preliminary studies. An earlier French study identified InsCCG243 as a cause of autosomal dominant diabetes. To determine the role of this variant in African Americans, we examined an additional population from North Carolina (n = 368) and a subset of African-American participants from the Atherosclerosis Risk in Communities (ARIC) study (n = 1,741). We also looked for segregation in 66 African-American families and for a role in insulin secretion in 112 nondiabetic subjects. InsCCG243 did not increase the risk of type 2 diabetes (P = 0.16 in North Carolina; P = 0.97 in the ARIC study) and did not segregate with type 2 diabetes in families. However, we found suggestive evidence for reduced insulin response to glucose (P = 0.05). Neither indirect measures of beta-cell mass nor beta-cell compensation were altered (P > 0.1). InsCCG243 does not act in a dominant, highly penetrant fashion in African Americans and is not a significant risk factor for type 2 diabetes in this population.
authors.affiliation: Endocrinology Section, Central Arkansas Veterans Healthcare System, Little Rock, Arkansas, USA. elbeinstevenc@uams.edu
authors.forename: Steven C
authors.initials: SC
authors.lastname: Elbein
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Wang
authors.forename: Mohammad A
authors.initials: MA
authors.lastname: Karim
authors.forename: Barry I
authors.initials: BI
authors.lastname: Freedman
authors.forename: Donald W
authors.initials: DW
authors.lastname: Bowden
authors.forename: Alan R
authors.initials: AR
authors.lastname: Shuldiner
authors.forename: Frederick L
authors.initials: FL
authors.lastname: Brancati
authors.forename: Wen Hong Linda
authors.initials: WH
authors.lastname: Kao
mesh_terms: D001741:Black or African American / Q000235:genetics*; D000595:Amino Acid Sequence; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D011392:Proline / Q000502:physiology*; D012307:Risk Factors; D015534:Trans-Activators / Q000235:genetics*
chemical_list: D018398:Homeodomain Proteins; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein; D011392:Proline