Contribution of known and unknown susceptibility genes to early-onset diabetes in scandinavia: evidence for heterogeneity.

Lindgren, C; Widén, E; Tuomi, T; Li, H; Almgren, P; Kanninen, T; Melander, O; Weng, J; Lehto, M; Groop, L

Women's Health Collection

Journal article

Contribution of known and unknown susceptibility genes to early-onset diabetes in scandinavia: evidence for heterogeneity.

Abstract:: In an attempt to identify novel susceptibility genes predisposing to early-onset diabetes (EOD), we performed a genome-wide scan using 433 markers in 222 individuals (119 with diabetes) from 29 Scandinavian families with > or =2 members with onset of diabetes < or =45 years. The highest nonparametric linkage (NPL) score, 2.7 (P < 0.01), was observed on chromosome 1p (D1S473/D1S438). Six other regions on chromosomes 3p, 7q, 11q, 18q, 20q, and 21q showed a nominal P value <0.05. Of the EOD subjects in these 29 families, 20% were GAD antibody positive and 68% displayed type 1 diabetes HLA risk alleles (DQB*02 or 0302). Mutations in maturity-onset diabetes of the young (MODY) 1-5 genes and the A3243G mitochondrial DNA mutation were detected by single-strand conformation polymorphism and direct sequencing. To increase homogeneity, we analyzed a subsample of five families with autosomal dominant inheritance of EOD (greater than or equal to two members with age at diagnosis < or =35 years). The highest NPL scores were found on chromosome 1p (D1S438-D1S1665; NPL 3.0; P < 0.01) and 16q (D16S419; NPL 2.9; P < 0.01). After exclusion of three families with MODY1, MODY3, and mitochondrial mutations, the highest NPL scores were observed on chromosomes 1p (D1S438; NPL 2.6; P < 0.01), 3p (D3S1620; NPL 2.2; P < 0.03), 5q (D5S1465; NPL 2.1; P < 0.03), 7q (D7S820; NPL 2.0; P < 0.03), 18q (D18S535; NPL 1.9; P < 0.04), 20q (D20S195; NPL 2.5; P < 0.02), and 21q (D21S1446; NPL 2.2; P < 0.03). We conclude that considerable heterogeneity exists in Scandinavian subjects with EOD; 24% had MODY or maternally inherited diabetes and deafness, and approximately 60% were GAD antibody positive or had type 1 diabetes-associated HLA genotypes. Our data also point at putative chromosomal regions, which could harbor novel genes that contribute to EOD.

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APA Style

Lindgren, C., Widén, E., Tuomi, T., Li, H., Almgren, P., Kanninen, T., Melander, O., Weng, J., Lehto, M., & Groop, L. (2002). Contribution of known and unknown susceptibility genes to early-onset diabetes in scandinavia: evidence for heterogeneity. Diabetes, 51(5), 1609–1617.

MLA Style

Lindgren, C, et al. “Contribution of Known and Unknown Susceptibility Genes to Early-Onset Diabetes in Scandinavia: Evidence for Heterogeneity.” Diabetes, vol. 51, no. 5, 2002, pp. 1609–17.

Chicago Style

Lindgren, C, E Widén, T Tuomi, et al. 2002. “Contribution of Known and Unknown Susceptibility Genes to Early-Onset Diabetes in Scandinavia: Evidence for Heterogeneity.” Diabetes 51 (5): 1609–17.
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