Polymorphism in the 5′ Flanking Region of the Human Insulin Gene: A Genetic Marker for Non-Insulin-Dependent Diabetes

Rotwein, Peter; Chirgwin, John M.; Province, Michael; Knowler, William C.; Pettitt, David J.; Cordell, Barbara; Goodman, Howard M.; Permutt, M. A.

doi:10.1056/nejm198301133080202

Cited by 134 publications

(66 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The present insulin receptor data supports findings in other racial populations that there is no association of this locus with Type 2 diabetes [27-291. The finding of the Class 3 allele of the insulin gene associating with Type 2 diabetes (relative risk= 4.7; 95% confidence limits of 2.0-11.2) supports similar studies in European Caucasoids [30,31] (UK and Denmark), Japanese subjects [32,33] and American Caucasoids in San Francisco [34]. However, other population studies of American Caucasoids in Los Angeles [171, Pima Indians [35], Punjabi Sikhs [27] and Naurian Indians [36] failed to find the same associations; indeed in one a Class 1 allele association was noted [17].…”

Section: Discussionsupporting

confidence: 82%

The genetic predisposition to fibrocalculous pancreatic diabetes

et al. 1989

View full text Add to dashboard Cite

Summary. Fibrocalculous pancreatic diabetes (previously known as tropical pancreatic diabetes) is a rare cause of diabetes confined to countries within the tropical belt. The aetiology of fibrocalculous pancreatic diabetes is thought to be environmental although the agent(s) is unknown. We have investigated a possible genetic basis of this disease by looking for restriction fragment length polymorphisms of genes implicated in the aetiology of diabetes rnellitus. Seventy-six Dravidian patients with fibrocalculous pancreatic diabetes were studied, and the restriction fragment length polymorphisms obtained compared to racially matched control subjects (n=94), patients with Type2 (non-insulin-dependent) diabetes (n=87) and Type 1 (insulin-dependent) diabetes (n = 58). No association of fibrocalculous pancreatic diabetes was found with restriction fragment length polymorphisms of the insulin receptor gene. Although no association of fibrocalculous pancreatic diabetes was found with polymorphism of the HLA DRc~/DQc~/DXct genes, an association was found with the Taq 1 restriction fragment length polymorphisms of the DQ[~ gene (DQ[~ T2/T6 present in 39% of patients with fibrocalculous pancreatic diabetes compared to 19% in control subjects; p = 0.01 ; corrected p value = 0.04) which is similar to that found in Type 1 but not Type 2 diabetes. An association of fibrocalculous pancreatic diabetes was also found with the hypervariable region in the 5-prime flanking region of the insulin gene; 40% of patients possessed the class 3 allele compared to 9.5% of control subjects p = 0.0001 ; corrected p value = 0.0008). In Type 2 diabetes, similar results were obtained with 33% subjects possessing the class 3 allele (t7 value compared to control subjects = 0.0005; corrected p value = 0.004). This study suggests that fibrocalculous pancreatic diabetes has a genetic component in its aetiology. Furthermore, its origin might be related to an individual with part of the genetic predisposition to diabetes (Type 1 or Type 2) who additionally has evidence of chronic calcific pancreatitis.

show abstract

Section: Discussionsupporting

confidence: 82%

The genetic predisposition to fibrocalculous pancreatic diabetes

et al. 1989

View full text Add to dashboard Cite

show abstract

“…The data support earlier claims of minor MHC influences in Type 2 diabetes in some ethnic groups [6,7], especially in age-of-onset effects and suggest, by the clear absence of a diabetes association, with the U and L restriction fragment types containing the insulin gene that the genes leading to diabetes in Nauru may differ from those claimed to lead to Type 2 diabetes in some Caucasoids [10,11].…”

Section: Discussionsupporting

confidence: 78%

“…This is despite reports of minor associations of Type 2 diabetes with HLA-A2 in both the Xhosa in Southern Africa [5] and the Pima of south-western United States [6] and with HLA-Bw61 in Indians from Uttar Pradesh resident in Fiji [7] and South Africa [8]. In Caucasoids, Type 2 diabetes is not associated with HLA antigens but possibly with DNA insertion sequences adjacent to the 5' end of the insulin gene [9,10,11]. This observation remains controversial since it has not been confirmed by some workers [12,13].…”

mentioning

confidence: 65%

Genetics of diabetes in Nauru: Effects of foreign admixture, HLA antigens and the insulin-gene-linked polymorphism

Serjeantson

Owerbach²,

Zimmet

et al. 1983

Diabetologia

View full text Add to dashboard Cite

Summary. Genetic factors play a major role in predisposition to diabetes in the Micronesian population of Nauru. In people aged 60years and older, 83% of full-blooded Nauruans were diabetic compared with 17% of those with ancestral foreign admixture, as detected by HLA typing. HLA distributions also showed a small increased risk for early onset of diabetes (< 46 years) associated with HLA-Bw22 (Bw56). Variation in the restriction fragment length of DNA near the insulin gene was found, but was not associated with diabetes. The distribution in fragment lengths, previously reported in Caucasoids, was observed in healthy Polynesians, Melanesians and Micronesians.

show abstract

“…Sequencing of the -23Hph1 single nucleotide polymorphism in Pima subjects. The A to T polymorphism that disrupts the Hph1 site CCACT at nucleotide 2,401 of the insulin gene (accession #V00565) was sequenced in the 660 members of parent-child "trios" described above and in 77 individuals previously typed for INS-VNTR (18,23). The PCR primers forward 5Ј-TCA GAAGAGGCCATCAAGCAGGT-3Ј and reverse 5Ј-CGCACAGGTGTTGGTTCA CAAA-3Ј were used to amplify a 574-bp fragment from genomic DNA, and the forward primer was further used for cycle sequencing.…”

Section: Methodsmentioning

confidence: 99%

The Insulin Gene Variable Number Tandem Repeat Class I/III Polymorphism Is in Linkage Disequilibrium With Birth Weight but Not Type 2 Diabetes in the Pima Population

et al. 2003

Self Cite

View full text Add to dashboard Cite

The insulin gene variable number tandem repeat (INS-VNTR) is proposed to exert pleiotropic genetic effects on birth weight and diabetes susceptibility. In our study, we examined the influence of a polymorphism in tight linkage disequilibrium with INS-VNTR (؊23Hph1) on birth weight and type 2 diabetes in the Pima population. A parent-offspring "trio" design was used to assess parent-of-origin effects and population stratification. The presence of the -23Hph1 T-allele was associated with lower birth weight (n ‫؍‬ 192; ؊140 g per copy of the T-allele; P ‫؍‬ 0.04), even after adjustment for effects of population stratification (P ‫؍‬ 0.03). The effects of paternally transmitted T-alleles were greater than those of maternally transmitted alleles (paternally transmitted: -250 g, P ‫؍‬ 0.05; maternally transmitted: -111 g, P ‫؍‬ 0.43), but this difference was not statistically significant (P ‫؍‬ 0.50). The ؊23Hph1 T-allele was associated with an increased prevalence of type 2 diabetes (P ‫؍‬ 0.009), which family-based association analysis suggested was attributable to population structure (P ‫؍‬ 0.04) without significant evidence of linkage disequilibrium between diabetes prevalence and genotype (P ‫؍‬ 0.86). Thus allelic variation of the INS gene is associated with lower birth weight and increased prevalence of type 2 diabetes. Significant linkage disequilibrium was found between -23Hph1 and birth weight but not type 2 diabetes, an observation that supports a potential functional role of INS polymorphisms in the regulation of birth weight. Diabetes 52: [187][188][189][190][191][192][193] 2003

show abstract

Polymorphism in the 5′ Flanking Region of the Human Insulin Gene: A Genetic Marker for Non-Insulin-Dependent Diabetes

Cited by 134 publications

References 37 publications

The genetic predisposition to fibrocalculous pancreatic diabetes

The genetic predisposition to fibrocalculous pancreatic diabetes

Genetics of diabetes in Nauru: Effects of foreign admixture, HLA antigens and the insulin-gene-linked polymorphism

The Insulin Gene Variable Number Tandem Repeat Class I/III Polymorphism Is in Linkage Disequilibrium With Birth Weight but Not Type 2 Diabetes in the Pima Population

Contact Info

Product

Resources

About