Evidence for a major gene for type II diabetes and linkage analyses with selected candidate genes in Mexican-Americans

Michael P. Stern, Braxton D. Mitchell, John Blangero, Laurie Reinhart, Candace M. Kammerer, Chantal R. Harrison, Patricia A. Shipman, Peter O'Connell, Marsha L. Frazier, Jean W. MacCluer

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Abstract

We have carried out two independent family studies in low-income Mexican- Americans from San Antonio, Texas. In the first study, probands were ascertained at random without regard to any medical condition (658 examined individuals from 50 families), and in the second study, probands were subjects with type II diabetes identified in a prior epidemiological survey (523 examined individuals from 29 families). Pedigrees ranging in size from 2 to 45 family members (median 11) in the first study and from 2 to 50 family members (median 12) in the second study were examined. Diabetes was diagnosed according to World Health Organization criteria. In both sets of families, segregation analyses revealed support for a major gene with an autosomal dominant mode of inheritance influencing early age of onset of diabetes. Non- Mendelian inheritance was rejected in both data sets. Individuals with the early age of onset allele bad a mean age of diabetes onset of 51 years in the first data set and 60 years in the second data set. In the first data set, the major gene accounted for ~70% of the phenotypic variance in age of onset of diabetes, and there were no residual family effects once the major gene effect was taken into account. In the second data set, the major gene accounted for ~50% of the phenotypic variance, and residual family effects were statistically significant. Linkage analyses were performed with 11 candidate genes, and tight linkage with diabetes was rejected for Rh blood group, glucose transporter 2, fatty acid-binding protein, tumor necrosis factor β, glucokinase, and lipoprotein lipase. A logarithm of odds (LOD) score of 0.92 at a recombination fraction of 0.05 was observed for insulin receptor substrate 1. This LOD score corresponds to a χ2 of 4.24 (P = 0.039).

Original languageEnglish (US)
Pages (from-to)563-568
Number of pages6
JournalDiabetes
Volume45
Issue number5
StatePublished - May 1996

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Type 2 Diabetes Mellitus
Age of Onset
Genes
Glucokinase
Insulin Receptor Substrate Proteins
Fatty Acid-Binding Proteins
Facilitative Glucose Transport Proteins
Lipoprotein Lipase
Pedigree
Blood Group Antigens
Genetic Recombination
Blood Glucose
Tumor Necrosis Factor-alpha
Alleles
Datasets

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Stern, M. P., Mitchell, B. D., Blangero, J., Reinhart, L., Kammerer, C. M., Harrison, C. R., ... MacCluer, J. W. (1996). Evidence for a major gene for type II diabetes and linkage analyses with selected candidate genes in Mexican-Americans. Diabetes, 45(5), 563-568.

Evidence for a major gene for type II diabetes and linkage analyses with selected candidate genes in Mexican-Americans. / Stern, Michael P.; Mitchell, Braxton D.; Blangero, John; Reinhart, Laurie; Kammerer, Candace M.; Harrison, Chantal R.; Shipman, Patricia A.; O'Connell, Peter; Frazier, Marsha L.; MacCluer, Jean W.

In: Diabetes, Vol. 45, No. 5, 05.1996, p. 563-568.

Research output: Contribution to journalArticle

Stern, MP, Mitchell, BD, Blangero, J, Reinhart, L, Kammerer, CM, Harrison, CR, Shipman, PA, O'Connell, P, Frazier, ML & MacCluer, JW 1996, 'Evidence for a major gene for type II diabetes and linkage analyses with selected candidate genes in Mexican-Americans', Diabetes, vol. 45, no. 5, pp. 563-568.
Stern MP, Mitchell BD, Blangero J, Reinhart L, Kammerer CM, Harrison CR et al. Evidence for a major gene for type II diabetes and linkage analyses with selected candidate genes in Mexican-Americans. Diabetes. 1996 May;45(5):563-568.
Stern, Michael P. ; Mitchell, Braxton D. ; Blangero, John ; Reinhart, Laurie ; Kammerer, Candace M. ; Harrison, Chantal R. ; Shipman, Patricia A. ; O'Connell, Peter ; Frazier, Marsha L. ; MacCluer, Jean W. / Evidence for a major gene for type II diabetes and linkage analyses with selected candidate genes in Mexican-Americans. In: Diabetes. 1996 ; Vol. 45, No. 5. pp. 563-568.
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AU - Kammerer, Candace M.

AU - Harrison, Chantal R.

AU - Shipman, Patricia A.

AU - O'Connell, Peter

AU - Frazier, Marsha L.

AU - MacCluer, Jean W.

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N2 - We have carried out two independent family studies in low-income Mexican- Americans from San Antonio, Texas. In the first study, probands were ascertained at random without regard to any medical condition (658 examined individuals from 50 families), and in the second study, probands were subjects with type II diabetes identified in a prior epidemiological survey (523 examined individuals from 29 families). Pedigrees ranging in size from 2 to 45 family members (median 11) in the first study and from 2 to 50 family members (median 12) in the second study were examined. Diabetes was diagnosed according to World Health Organization criteria. In both sets of families, segregation analyses revealed support for a major gene with an autosomal dominant mode of inheritance influencing early age of onset of diabetes. Non- Mendelian inheritance was rejected in both data sets. Individuals with the early age of onset allele bad a mean age of diabetes onset of 51 years in the first data set and 60 years in the second data set. In the first data set, the major gene accounted for ~70% of the phenotypic variance in age of onset of diabetes, and there were no residual family effects once the major gene effect was taken into account. In the second data set, the major gene accounted for ~50% of the phenotypic variance, and residual family effects were statistically significant. Linkage analyses were performed with 11 candidate genes, and tight linkage with diabetes was rejected for Rh blood group, glucose transporter 2, fatty acid-binding protein, tumor necrosis factor β, glucokinase, and lipoprotein lipase. A logarithm of odds (LOD) score of 0.92 at a recombination fraction of 0.05 was observed for insulin receptor substrate 1. This LOD score corresponds to a χ2 of 4.24 (P = 0.039).

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