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M I McCarthy

Publications and source records attributed to M I McCarthy.

64 records · Page 4Linked to original sources
PubMed1994

Apolipoprotein D gene polymorphism: a new genetic marker for type 2 diabetic subjects in Nauru and south India.

Type 2 diabetes is characterized by abnormalities in both glucose and lipoprotein metabolism and genes involved in lipid metabolism are legitimate candidates for involvement in Type 2 diabetes. We have previously reported an association in Nauruans between a Taq 1 polymorphism of the apolipoprotein D gene (apo D) and Type 2 diabetes. In this study these findings were investigated further in the Nauruan population as well as two other ethnic groups. In South Indian subjects, there was a significant difference in genotype distribution of apo D genotypes between diabetic subjects (n = 110) and controls (n = 88; p = 0.004) which was similar to that previously found in the Nauruan subjects. No such association was seen in elderly Finnish subjects (diabetic n = 69; impaired glucose tolerance n = 26 and normal glucose tolerance n = 31). Linkage between the apo D polymorphism and diabetes in 12 Nauruan families was only excluded under a highly penetrant dominant model and was unlikely under other single gene models. Since the beta cell glucose transporter gene (Glut 2) is found in a similar chromosomal location to apo D, South Indian subjects (diabetic n = 95 and controls n = 56) were typed at this locus. No association between diabetes and the Glut 2 Taq I polymorphism was found in the South Indian subjects. Furthermore, there was no evidence of linkage disequilibrium between the apo D and Glut 2 genes. In conclusion, apo D might act as a modifying gene for Type 2 diabetes in some ethnic groups.

Adolescent↗
PubMed1994

Glucokinase gene polymorphisms: a genetic marker for glucose intolerance in a cohort of elderly Finnish men.

Although mutations in the glucokinase gene are implicated in the pathogenesis of glucose intolerance in pedigrees with maturity-onset diabetes of the young, the role of such mutations in typical Type 2 diabetes is poorly characterized. We studied a cohort of elderly men born (between 1900 and 1919) in two Finnish communities and exhibiting a continuous spectrum of glucose tolerance at assessments made in 1984 and 1989. Individuals were typed at two polymorphic microsatellites straddling the glucokinase gene, GCK(3') (n = 169) and GCK(5') (n = 166): these two markers were in linkage equilibrium in this cohort. Significant associations between alleles at the GCK(3') marker and glucose tolerance were evident (p = 0.002), the frequency of the (z + 2) allele rising from zero in control subjects (n = 88 chromosomes) to 6.5% (n = 62) in subjects with impaired tolerance and 12.2% (n = 188) in subjects with diabetes. Mean 2-h glucose levels were 10.5 (9.6-11.4, 95% confidence interval) mmol l-1 in individuals with the (z + 2) allele and 8.1 (7.6-8.7) mmol l-1 in those without (p = 0.01, corrected for multiple comparisons). No association was evident between GCK(5') alleles and glucose tolerance. The GCK(3') microsatellite is a marker for abnormal glucose tolerance in this cohort of elderly Finnish men.

Aged↗
PubMed1993

Positive association in the absence of linkage suggests a minor role for the glucokinase gene in the pathogenesis of type 2 (non-insulin-dependent) diabetes mellitus amongst south Indians.

Mutations of the glucokinase gene have been implicated in the development of glucose intolerance in pedigrees with maturity-onset diabetes of the young. However, the contribution of the glucokinase gene to the aetiology of common Type 2 (non-insulin-dependent) diabetes mellitus is uncertain. We have studied the role of the glucokinase gene in the pathogenesis of Type 2 diabetes in South Indians, using both population-association and linkage methodology. A pair of CA-repeat sequences (GCK(3') and GCK(5')) straddling the glucokinase gene were employed as markers, each subject being typed using the polymerase chain reaction and polyacrylamide gel electrophoresis. Comparisons of allele frequencies at these markers were made between 168 Type 2 diabetic subjects and 70 racially-matched control subjects. No differences in allele frequencies were apparent at the GCK(5') marker; however, there were significant differences in allele frequencies at the GCK(3') marker between the Type 2 diabetic subjects and control subjects (chi 2 = 11.6, df = 3, p = 0.009) with an increase of the z allele (78.0% vs 66.4%) and a decrease of the z + 2 allele (13.7% vs 25.0%) amongst the diabetic subjects. Linkage between glucose intolerance and the glucokinase gene was studied in 53 nuclear pedigrees under a variety of genetic models. Linkage was excluded (lod score < -2) at a recombination fraction of zero under five of the ten models used and highly unlikely (-2 < lod score < -1) under the others. The combination of positive association and negative linkage suggests that glucokinase acts as a minor gene influencing the development of Type 2 diabetes within this population.

Adult↗
PubMed1993

Predicting relapse after transsphenoidal surgery for Cushing's disease.

Although selective transsphenoidal surgery is an effective treatment for pituitary-dependent Cushing's syndrome the definition of cure as distinct from improvement is unclear. Complete tumor removal should be associated with very low serum cortisol levels because of long-term suppression of normal corticotrophs but the optimum timing of this investigation after surgery has not been established. Eleven consecutive patients with surgical and histological confirmation of a corticotroph adenoma removed at transsphenoidal surgery for proven Cushing's disease were studied with 0900 h serum cortisol levels at 5-14 days and 6-12 weeks postoperatively. Patients were maintained on hydrocortisone 10 mg three times daily (final dose at 1800 h) pending recovery of the hypothalamic-pituitary axis which was assessed by periodic short tetracosactrin tests and continued remission of the condition was confirmed by low dose dexamethasone suppression testing. All patients achieved clinical resolution of their disease but four subsequently developed biochemical evidence of recurrence with incomplete suppression on low dose dexamethasone testing at 2-48 months after surgery. These patients had 0900 h serum cortisol levels of 124, 95, 186, and 265 nmol/L at 5-14 days and 334, 52, 130, and 240 nmol/L at 6-12 weeks postoperatively. The remaining seven patients, who are in remission after 8-83 (median 24) months of follow-up, demonstrated 0900 h serum cortisol levels of 30-75 (median 31) nmol/L at 5-14 days but lower levels at 6-12 weeks (< 20 nmol/L in three patients and 22, 30, 30, and 33 nmol/L in the remainder). In this series, serum cortisol measurements at 6-12 weeks after transsphenoidal surgery for Cushing's disease are lower than levels obtained within 2 weeks of surgery and appear to give better discrimination of continuing remission; levels less than 35 nmol/L suggest a favorable long-term outcome.

Adenoma↗
PubMed1992

The islet amyloid polypeptide gene and non-insulin-dependent diabetes mellitus in south Indians.

Islet amyloid polypeptide (IAPP), otherwise called amylin, is the monomeric component of islet amyloid. Deposition of this amyloid is a characteristic feature of non-insulin-dependent diabetes mellitus in humans and may play a role in the pathogenesis of the disease. As such, abnormalities in the structure or expression of the IAPP gene might contribute to the inheritance of this condition. The IAPP gene was studied in a well-characterised population of 62 unrelated Dravidian subjects with non-insulin-dependent diabetes mellitus and 56 normal Dravidian controls, using a restriction fragment length polymorphism generated by PvuII digestion. Genotype and allele frequencies did not differ between diabetic subjects and controls. Taken together with recent findings in Europid and other racial groups, an abnormality of the IAPP gene is highly unlikely to represent a major gene for the development of non-insulin-dependent diabetes mellitus.

Alleles↗
PubMed1992

The genetics of non-insulin-dependent diabetes mellitus in south India: an overview.

Non-insulin-dependent diabetes mellitus affects approximately 10% of urban Indian and Indian migrant populations and as such carries major health implications for these groups. Whilst a strong genetic component to the aetiology of non-insulin-dependent diabetes mellitus is incontestable, progress in identifying the specific genetic determinants involved in its pathogenesis has been slow. In studies of South Indian pedigrees, preliminary segregation analysis indicates that non-insulin-dependent diabetes mellitus is likely to be a polygenic disease. A number of candidate genes have been studied with the aim of demonstrating either association or linkage with the disease; in South Indians the only positive results thus far have been associations between non-insulin-dependent diabetes mellitus and the genes for insulin, apolipoprotein D and complement component C4B. However, it seems likely that these genes contribute only a small proportion of the genetic susceptibility to non-insulin-dependent diabetes mellitus in this ethnic group and that the major genes underlying glucose intolerance remain to be determined.

Apolipoproteins↗
PubMed1991

Genetics of non-insulin dependent diabetes mellitus.

It is probable that NIDDM has a multifactorial origin in which environmental factors hasten the progression of the disease in genetically predisposed individuals. The importance of the genetic contribution to NIDDM has been established by the study of certain inbred populations, the almost 100% concordance of disease in monozygotic twins and by familial clustering. However, progress in identifying specific genetic factors involved in NIDDM has been slow and no consistent evidence has emerged supporting a major aetiological role for any of the genes so far studied. This may be due in part to methodological problems encountered in the identification of such disease susceptibility genes.

Age Factors↗
PubMed1990

Familial acromegaly: studies in three families.

Acromegaly is usually regarded as a disease which arises sporadically except on those rare occasions in which it occurs as one component of an inherited pluriglandular syndrome. Familial acromegaly occurring in isolation has been reported only rarely. We have studied three families in each of which two first-degree relatives have developed acromegaly without clinical evidence of other endocrinopathies, in order to clarify the relationship of familial acromegaly to multiple endocrine neoplasia, type 1 (MEN 1). No further subclinical cases of acromegaly have been detected in those first-degree relatives of the index cases who were screened. In two of the families, we have found no evidence of abnormal pancreatic or parathyroid function either in the acromegalic index cases or their asymptomatic relatives: a diagnosis of MEN 1 is therefore effectively excluded. In the third family, the presence of multiple subcutaneous lipomata in several members of the family and elevation of PTH levels in two (normocalcaemic) acromegalic index cases, might indicate a highly atypical presentation of MEN 1. None of the six acromegalic index cases had elevations of circulating growth hormone releasing hormone levels. We conclude that isolated familial acromegaly may be more common than has hitherto been realized and that, in these families at least, ectopic production of growth hormone releasing hormone is not responsible.

Acromegaly↗