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    Diabetes. 2006 Oct;55(10):2909-14.

    Role of a proline insertion in the insulin promoter factor 1 (IPF1) gene in African Americans with type 2 diabetes.

    Elbein SC, Wang X, Karim MA, Freedman BI, Bowden DW, Shuldiner AR, Brancati FL, Kao WH.

    Endocrinology Section, Central Arkansas Veterans Healthcare System, Little Rock, Arkansas, USA. elbeinstevenc@uams.edu

    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.

    PMID: 17003361 [PubMed - indexed for MEDLINE]

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