Availability of type II diabetic families for detection of diabetes susceptibility genes.
Type II diabetes is a familial disorder, as evidenced by the increased prevalence in monozygotic cotwins and first-degree relatives of affected subjects; however, its genetic etiology is largely unknown. Well-characterized pedigrees are an essential resource for the study of susceptibility genes for type II diabetes. This study describes a 5-yr search for type II diabetic families in Oxfordshire, U.K. We interviewed 950 type II diabetic subjects concerning the availability of first-degree relatives; 127 Caucasian families ascertained through a proband with type II diabetes were studied, and 589 first-degree relatives were characterized. Three large pedigrees with maturity-onset diabetes of the young, and 8 multiplex multigenerational type II diabetic pedigrees were identified. We identified 12 sib-pairs in which both siblings had type II diabetes; however, only 7 sib-pairs had both parents alive, and 2 of these had both parents affected. If one also considers one sib having diabetes and one sib having glucose intolerance as being an affected sib-pair, we identified 30 sib-pairs of which 7 had both parents affected and probably had bilineal inheritance. We identified 76 complete nuclear families with both parents and offspring available for study, but only 6 were of optimal structure for linkage analysis. In conclusion, multiplex pedigrees and type II diabetic sib-pairs with living parents are uncommon, and their ascertainment requires a substantial investment of resources. Large-scale collaborative multicenter initiatives would be needed to collect a large resource of family material for the study of susceptibility genes for type II diabetes.
Diabetes Research Laboratories, Radcliffe Infirmary, Oxford, UK.
J T
JT
Cook
R C
RC
Page
S
S
O'Rahilly
J
J
Levy
R
R
Holman
B
B
Barrow
A T
AT
Hattersley
A G
AG
Shaw
J S
JS
Wainscoat
R C
RC
Turner
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology* / Q000209:etiology / Q000235:genetics*; D004198:Disease Susceptibility; D005192:Family Health; D005260:Female; D005796:Genes / Q000235:genetics*; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D015995:Prevalence; D006113:United Kingdom / Q000453:epidemiology