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Genetic variability in insulin action inhibitor Ikkbeta (IKBKB) does not play a major role in the development of type 2 diabetes.

Abstract
Recent evidence indicates that IkappaB kinase beta (Ikkbeta) may be a mediator of acquired forms of insulin-resistance. In this study, we examined whether genetic variability at the Ikkbeta locus (IKBKB) contributes to the development of genetic forms of early-onset type 2 diabetes transmitted with an autosomal dominant mode of inheritance. Linkage with four markers flanking the IKBKB gene was evaluated in 32 multigenerational families. Included in the study were 233 diabetic (mean age at Dx = 37 +/- 18) and 152 nondiabetic subjects. The overall LOD scores were negative (-54.9 and -46.2 on the centromeric and telomeric sides, respectively) indicating that variability in IKBKB was not a major determinant of diabetes in these families. Positive values, however, were observed for selected pedigrees. All 17 families for which linkage with the IKBKB locus could not be excluded were screened for sequence differences in the 22 exons and 1.6 kb of the 5' flanking region by dideoxyfingerprinting or direct sequencing. Polymorphisms were identified in the 5' flanking region (-1775del/insC and -1547T > A), exon 11 (c.1083A > G, L361L) and in intron 12 (IVS12+14t > a). However, no mutations segregating with diabetes could be found in these families. Furthermore, all four polymorphisms had similar allele frequencies in the 32 family probands, 171 individuals with common, later-onset type 2 diabetes, and 182 nondiabetic controls. We conclude that sequence differences in the IKBKB gene do not play a major role in either early-onset, autosomal dominant type 2 diabetes, or common forms with a later-onset.
AuthorsClaudia Menzaghi, Nattachet Plengvidhya, Xiaowei Ma, James H Warram, Steven E Shoelson, Alessandro Doria
JournalThe Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 87 Issue 4 Pg. 1894-7 (Apr 2002) ISSN: 0021-972X [Print] United States
PMID11932336 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Protein Serine-Threonine Kinases
  • CHUK protein, human
  • I-kappa B Kinase
  • IKBKB protein, human
  • IKBKE protein, human
Topics
  • Age of Onset
  • Diabetes Mellitus, Type 2 (epidemiology, genetics)
  • Gene Frequency
  • Genes, Dominant
  • Genetic Linkage
  • Genetic Testing
  • Genetic Variation
  • Humans
  • I-kappa B Kinase
  • Polymorphism, Genetic
  • Protein Serine-Threonine Kinases (genetics)
  • Reference Values

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