Association of amino acid variants in the activating transcription factor 6 gene (ATF6) on 1q21-q23 with type 2 diabetes in Pima Indians

Farook Thameem, Vidya S. Farook, Clifton Bogardus, Michal Prochazka

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Abstract

Activating transcription factor 6 (ATF6) is important for protective cell response to accumulation of unfolded and misfolded proteins in endoplasmic reticulum, and disturbances of this process can contribute to β-cell apoptosis. We analyzed the structural gene located within a region on 1q21-q23 linked with type 2 diabetes in several populations for variants in the Pima Indians. Functionally important segments of ATF6 were sequenced in 15 diabetic and 15 nondiabetic Pimas and representative single nucleotide polymorphisms (SNPs) tested for association with type 2 diabetes in 900-1,000 subjects. We identified 20 variants including three amino acid substitutions [Met(67)Val, Pro(145)Ala, and Ser(157)Pro]. Pro(145)Ala and Ser(157) Pro were in a complete linkage disequilibrium and showed a nominal association with type 2 diabetes (P = 0.05; odds ratio 2.3 [95% CI 1.0 -5.2]) and with 30-min plasma insulin during oral glucose tolerance test in 287 nondiabetic individuals (P = 0.045). Although the associations with type 2 diabetes and plasma insulin levels are marginal and their functional consequences are yet unknown, all three amino acid substitutions are located in a functionally important part of ATF6. Because these variants are not unique to the Pimas, it will be feasible to investigate their association with type 2 diabetes in other populations to better evaluate their significance for a predisposition to the disease.

Original languageEnglish (US)
Pages (from-to)839-842
Number of pages4
JournalDiabetes
Volume55
Issue number3
StatePublished - Mar 2006

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Activating Transcription Factor 6
Potassium Iodide
Type 2 Diabetes Mellitus
Amino Acids
Genes
Amino Acid Substitution
Insulin
Protein Unfolding
Linkage Disequilibrium
Glucose Tolerance Test
Endoplasmic Reticulum
Population
Single Nucleotide Polymorphism
Odds Ratio
Apoptosis

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Association of amino acid variants in the activating transcription factor 6 gene (ATF6) on 1q21-q23 with type 2 diabetes in Pima Indians. / Thameem, Farook; Farook, Vidya S.; Bogardus, Clifton; Prochazka, Michal.

In: Diabetes, Vol. 55, No. 3, 03.2006, p. 839-842.

Research output: Contribution to journalArticle

Thameem, Farook ; Farook, Vidya S. ; Bogardus, Clifton ; Prochazka, Michal. / Association of amino acid variants in the activating transcription factor 6 gene (ATF6) on 1q21-q23 with type 2 diabetes in Pima Indians. In: Diabetes. 2006 ; Vol. 55, No. 3. pp. 839-842.
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