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G A Hitman

Publications and source records attributed to G A Hitman.

119 records · Page 7Linked to original sources
PubMed1985

Are there genetic determinants for the glucose intolerance of acromegaly?

A genetic marker identifying the two parental insulin genes has been studied in 51 Caucasian acromegalics by Southern blot hybridization techniques using a cloned insulin gene probe. Two main DNA insertion classes were detected corresponding to the class 1 and class 3 alleles and thus the following genotypes were found: 1/1, 1/3 and 3/3. The acromegalics were subdivided depending on whether they had a normal (n = 30) or abnormal (n = 21) response to a 50 gm oral glucose tolerance test before treatment. The phenotype frequencies in the former group were 1/1, 43%; 1/3, 53%; and 3/3, 4%; and in the latter group the corresponding figures were 76%, 24% and 0%. The relative incidence of concordance of the phenotype 1/1 with abnormal glucose tolerance in acromegaly was 4.2. This phenotype is also associated with insulin dependent (Type 1) diabetes mellitus.

Acromegaly↗
PubMed1984

Diabetic hypertriglyceridaemia and related 5' flanking polymorphism of the human insulin gene.

A polymorphic DNA sequence was studied on the 5' flanking region of the human insulin gene in relation to diabetic lipaemia. The genotype frequencies in a control population (n = 52) were homozygous L 6%, heterozygous 54%, and homozygous S 40%. Corresponding genotype frequencies in a hypertriglyceridaemic group (n = 74) were 18%, 66%, and 16% (p less than 0.01; chi 2 test). When the hypertriglyceridaemic patients were divided on the basis of glucose tolerance the corresponding genotype frequencies in the diabetic subgroup (n = 23) were 39%, 52%, and 9% compared with 0%, 74%, and 26% in the non-diabetics (n = 34) (p less than 0.001; chi 2 test). These findings suggest that the homozygous L genotype may confer susceptibility to diabetic hypertriglyceridaemia.

Adult↗
PubMed1984

Insulin and apolipoprotein A-1/C-III gene polymorphisms relating to hypertriglyceridaemia and diabetes mellitus.

Two gene specific probes have been used to identify polymorphic DNA loci on chromosome 11 close to the insulin and apoprotein A-1 genes in a genetic analysis of hypertriglyceridaemic patients with and without co-existing diabetes. Of the 45 patients studied with both probes, 15 were diabetic of whom nine possessed class 3/3 insulin polymorphism genotypes, compared with none in the non-diabetic group (p less than 0.001; chi 2 test). In contrast, an uncommon apolipoprotein A-1 polymorphism was found to be equally distributed in the diabetic and the non-diabetic patients. No co-segregation of these two particular genetic polymorphisms was found in either patient group. The differing associations of the two disease-related polymorphism genotypes in patients with hypertriglyceridaemia with or without co-existing diabetes may possibly reflect differing aetiologies of the hyperlipidaemia.

Adult↗
PubMed1984

Polymorphisms in the 5'-flanking region of the insulin gene and non-insulin-dependent diabetes.

DNA insertions in the 5'-flanking region of the insulin gene have been studied by Southern-blot-hybridization techniques using a cloned gene probe in 159 unrelated Caucasians. Subjects homozygous for a large DNA insertion at this locus were found to have a higher risk of concurrence of non-insulin-dependent diabetes (NIDD) than controls (P less than 0.01). Analysis of a single large NIDD pedigree (n = 67 in four generations; 11 diabetic subjects) showed no linkage between the size of DNA inserts and diabetes (Lod score = -5.7), suggesting a separate diabetogenic locus (or loci) in this family.

DNA Transposable Elements↗
PubMedDate not supplied

Type 1 diabetes in the offspring does not increase the risk of parental type 2 diabetes in South Indians.

OBJECTIVES: (a) To study whether there was an increased prevalence of glucose intolerance in the parents of probands with Type 1 diabetes and (b) to look for any possible link between the glucose intolerance in the parents with HLA-DQB1 alleles transmitted in excess to the Type 1 diabetes offspring. Study Design and Methods From 215 families of South Indian Type 1 diabetes probands, 336 parents (170 fathers, age 30-70 years; 166 mothers, age 23-72 years) were studied by oral glucose tolerance test (GTT). Glucose intolerance in the parents was compared with the population data available. HLA-DQB1 alleles in 170 of the families were studied by the Olerup method (based on sequence specific primers) and the transmission disequilibrium test (TDT) was used to determine the Type 1 diabetes-associated DQB1 alleles. RESULTS: Among the parents 11.2% had Type 2 diabetes which was similar to the population data of 11.6%. However there was a male predominence among the diabetic parents (chi(2)=7.0, p=0.008), while in the population there was a female predominence. Prevalence of IGT was significantly more among the parents (13.6%) compared with the population data (9.1%) (chi(2)=6.43, p=0.011). Both HLA-DQB1*0201 (p<0.0001) and DQB1*0302 (p=0.0001) were positively associated with Type 1 diabetes in the probands although 21% of the probands possessed neither DQB1*0201 or DQB1*0302. The distribution of glucose tolerance categories in the parents of the probands differed according to the presence of DQB1*0302 (p= 0.035) whilst no such differences existed for DQB1*0201. CONCLUSIONS: In summary, the presence of Type 1 diabetes in the South Indian offspring does not predict a higher occurrence of Type 2 diabetes in the parents. However, there is an increased occurrence of impaired glucose tolerance (IGT) among the parents. Family based studies demonstrate increased transmission of HLA-DQB1*0201 and HLA-DQB1*0302 with Type 1 diabetes similar to North American and European Caucasian subjects. Furthermore, HLA-DQB1*0302 may be a minor determinant of glucose tolerance in parents of offspring with Type 1 diabetes.

Adolescent↗
PubMedDate not supplied

Pancreatitis in fibrocalculous pancreatic diabetes mellitus is not associated with common mutations in the trypsinogen gene.

BACKGROUND: A distinct type of pancreatitis associated with diabetes, termed fibrocalculous pancreatic diabetes (FCPD), has been reported in tropical developing countries including Bangladesh. The molecular basis for autosomal dominant hereditary pancreatitis (HP) has recently been attributed to mutations in exons 2 and 3 of the trypsinogen gene. We have investigated the hypothesis that mutations in the aforementioned exons of this gene might also predispose to FCPD. METHODS: Seventy Bangladeshi and 50 South Indian unrelated FCPD patients and seven South Indian families with FCPD probands were studied. Pancreatic calcification was confirmed by abdominal X-ray, ultrasound and/or ERCP. Established mutations of exons 2 and 3 of the trypsinogen gene were studied in these subjects by PCR-RFLP analysis and DNA sequencing. RESULTS: The mutations found in hereditary pancreatitis were not observed in this collection of FCPD subjects, and complete DNA sequencing of exons 2 and 3 of the fourth cationic trypsinogen gene also excluded any new mutations. CONCLUSIONS: These results indicate that chronic pancreatitis of FCPD is unlikely to be caused by common mutations in the trypsinogen gene.

Adult↗
PubMedDate not supplied

Family association studies of markers on chromosome 2q and Type 1 diabetes in subjects from South India.

BACKGROUND: Several Type 1 diabetes susceptibility loci have been located to chromosome 2q12-21. However, results have not always been consistent and this may reflect study design and the population analysed. We have used a family-based design to look for an association between Type 1 diabetes and markers located to 2q12-21. METHODS: Ninety-one South Indian families consisting of subjects with Type 1 diabetes and their parents were genotyped for eight polymorphic markers localised to 2q12-21, which includes the interleukin-1 gene cluster. Radiation hybrid mapping was used to localise the map position of D2S308 and D2S363 on 2q12-21. The extended transmission disequilibrium test was used for statistical analysis. RESULTS: No associations were found between Type 1 diabetes and markers located in and around the interleukin-1 gene cluster or the interleukin-1 Type 1 receptor. In contrast, a suggestive association was found between Type 1 diabetes and two closely-linked markers telomeric of the interleukin-1 gene cluster (D2S308 and D2S363, separated by 3.3 cR) (p=0.004 and p=0.002, respectively). CONCLUSION: This preliminary study suggests that a locus close to D2S308 and D2S363 is involved in the aetiology of Type 1 diabetes in the South Indian population.

Adolescent↗
PubMedDate not supplied

New HLA DNA polymorphisms associated with autoimmune diseases.

Certain class II determinants of the human histocompatibility locus antigens (HLA) have been implicated in the aetiology of several autoimmune diseases, including rheumatoid arthritis (RA) and insulin-dependent diabetes mellitus (IDDM). HLA-Dw4 was the first HLA determinant found to be significantly increased in RA patients compared with controls, while Dw4 and Dw3 were found to be significantly increased in IDDM patients. When the HLA-DR system was defined, RA patients were found to have an increased frequency of DR4 and IDDM patients an increased incidence of both DR4 and DR3 compared with controls. As the HLA-Dw specificities are narrower than the serologically defined DR specificities, it was of specific interest to the present study that Dw4, Dw10, Dw13, Dw14, Dw15 and DKT2 are included in DR4. We describe here new restriction fragment length polymorphisms (RFLPs) and, together with the newly described serologically defined DQ specificity TA10, test their prevalence and associations in controls and diseased patients. We find that the newly characterized DNA bands are present at a much higher frequency in RA and IDDM patients than in controls. These findings may lead to a greater understanding of the pathogenesis of such diseases.

Arthritis, Rheumatoid↗
PubMedDate not supplied

A genetic analysis of type 2 (non-insulin-dependent) diabetes mellitus in Punjabi Sikhs and British Caucasoid patients.

A genetic analysis of diabetic and non-diabetic Punjabi Sikhs (n = 164) was made for markers of non-insulin-dependent diabetes mellitus using insulin receptor, insulin, and HLA-D alpha chain gene probes. Additionally British Caucasoids (n = 163) were studied using the insulin receptor probe. Insulin receptor gene restriction fragment length polymorphisms were defined using Southern blot techniques and the restriction enzyme Bgl II and BAm Hl. In Punjabi Sikhs and British Caucasoids neither of the restriction fragment length polymorphisms distinguished non-insulin-dependent diabetes mellitus subjects from controls. In the Sikhs no association with non-insulin-dependent diabetes mellitus was seen with the hypervariable region of the insulin gene or with HLA-DR/DQ/DX alpha chain restriction fragment length polymorphisms. We therefore conclude that despite the high prevalence of non-insulin-dependent diabetes mellitus in Asians we were unable to find any genetic markers for this disease using the available cloned gene probes.

Diabetes Mellitus, Type 2↗