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

Claudia Menzaghi, Nattachet Plengvidhya, Ma Xiaowei, James H. Warram, Steven E. Shoelson, Alessandro Doria

Research output: Contribution to journalArticle

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Abstract

Recent evidence indicates that IκB kinase β (Ikkβ) may be a mediator of acquired forms of insulin-resistance. In this study, we examined whether genetic variability at the Ikkβ 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.

Original languageEnglish
Pages (from-to)1894-1897
Number of pages4
JournalJournal of Clinical Endocrinology and Metabolism
Volume87
Issue number4
DOIs
Publication statusPublished - 2002

Fingerprint

I-kappa B Kinase
Medical problems
Type 2 Diabetes Mellitus
Insulin
5' Flanking Region
Polymorphism
Exons
Genes
Pedigree
Gene Frequency
Introns
Insulin Resistance
Phosphotransferases
Mutation

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

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Genetic variability in insulin action inhibitor Ikkβ (IKBKB) does not play a major role in the development of type 2 diabetes. / Menzaghi, Claudia; Plengvidhya, Nattachet; Xiaowei, Ma; Warram, James H.; Shoelson, Steven E.; Doria, Alessandro.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 87, No. 4, 2002, p. 1894-1897.

Research output: Contribution to journalArticle

Menzaghi, Claudia ; Plengvidhya, Nattachet ; Xiaowei, Ma ; Warram, James H. ; Shoelson, Steven E. ; Doria, Alessandro. / Genetic variability in insulin action inhibitor Ikkβ (IKBKB) does not play a major role in the development of type 2 diabetes. In: Journal of Clinical Endocrinology and Metabolism. 2002 ; Vol. 87, No. 4. pp. 1894-1897.
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