Biomedical subjects

L J Brown

Publications and source records attributed to L J Brown.

At least 73 records · Page 4Linked to original sources

PubMed1996

Genetic mapping and chromosome localization of the rat mitochondrial glycerol-3-phosphate dehydrogenase gene, a candidate for non-insulin-dependent diabetes mellitus.

The mitochondrial FAD-dependent glycerol-3-phosphate dehydrogenase (mtGPD) plays an important role in the regulation of insulin secretion and has been postulated as a candidate responsible for the pathogenesis of non-insulin-dependent diabetes mellitus (NIDDM) in humans as well as in rodent models of NIDDM. Recent molecular genetic studies of the Goto-Kakizaki (GK) rat model of NIDDM have identified loci linked to NIDDM. To elucidate whether rat mtGPD might play a role in the pathogenesis of NIDDM, the rat mtGPD gene (Gpd2) was cloned, and a genetic marker for Gpd2 was developed. The gene mapped to the region of rat chromosome 3 that contains a region linked to NIDDM in the GK rat. Fluorescence in situ hybridization was also carried out to verify the map position.

Animals↗

PubMed1996

Structural organization and mapping of the human mitochondrial glycerol phosphate dehydrogenase-encoding gene and pseudogene.

Mitochondrial glycerol phosphate dehydrogenase (mtGPD) is the rate-limiting enzyme in the glycerol phosphate shuttle, which is thought to play an important role in cells that require an active glycolytic pathway. Abnormalities in mtGPD have been proposed as a potential cause for non-insulin-dependent diabetes mellitus. To facilitate genetic studies, we have isolated genomic clones containing the coding regions of the human mtGPD-encoding gene (GPDM). The gene contains 17 exons and is estimated to span more than 80 kb. All splice junctions contain GT/AG consensus sequences. Introns interrupt the sequences encoding the leader peptide, the FAD-binding site, the calcium-binding regions, and a conserved central element postulated to play a role in glycerol phosphate binding. Fluorescence in situ hybridization was used to map this gene to chromosome 2, band q24.1. A retropseudogene was identified and mapped to chromosome 17.

Base Sequence↗

PubMed1996

Calcium activation of mitochondrial glycerol phosphate dehydrogenase restudied.

cDNAs which encode the rat testis and pancreatic islet mitochondrial glycerol phosphate dehydrogenase (mGPD) (EC 1.1.99.5), the key enzyme of the glycerol phosphate shuttle, were recently cloned and sequenced and found to contain calmodulin-like calcium-binding sequences, thus explaining the widely observed calcium activation of the enzyme from many tissues of higher eukaryotes. mGPD activity and protein, as judged from Western analysis, appear to be most abundant in testis and pancreatic islets in the rat. mGPD is known to be located within the inner mitochondrial membrane. At a physiologic concentration of glycerol phosphate (75 microM), half maximal activity of Triton X-100-solubilized testis mGPD was seen in the presence of 0.1-0.25 microM free calcium. Calcium (10(-6)-10(-5) M) lowered the Km of mGPD from 2.5 mM glycerol phosphate (islet mGPD) and 3.2 mM glycerol phosphate (testis mGPD) to 0.4 mM glycerol phosphate. Calcium activation of mGPD from both testis and islets was not prevented by calmodulin inhibitors, which is consistent with mGPD possessing regions that can mediate its own activation by calcium. 45Calcium overlay experiments, in which proteins were separated by SDS-polyacrylamide gel electrophoresis, blotted onto nitrocellulose membranes, and probed with 45Ca, showed that mGPD is a major calcium-binding protein in testis mitochondrial membranes. A hydropathy plot suggested that the mature mGPD protein has three transmembrane helices. The first membrane-spanning region coincides with the FAD site and thus this site is placed within the membrane. The hydropathy analysis indicated that the calcium-binding region and the putative glycerol phosphate-binding site lie outside the membrane exposed to the cytosolic environment. This is consistent with earlier biochemical evidence which indicated that these sites are situated outside the membrane (M. Klingenberg, Eur. J. Biochem. 13, 247-252, 1970). This suggests that cytosolic calcium can regulate mGPD activity. Since simultaneous oscillations in electrical activity, cytosolic calcium, glycolysis, and insulin release occur in the pancreatic beta cell, mGPD activity might also fluctuate and allow the glycerol phosphate shuttle to participate in glycolytic oscillations.

Amino Acid Sequence↗

PubMed1996

Self-reported changes in capillary glucose and insulin requirements during the menstrual cycle.

Perimenstrual changes in glycaemic control and insulin requirements have been reported in Type 1 diabetes. A population-based sample of 124 women with Type 1 diabetes, aged 18 to 40 years, were questioned regarding perimenstrual changes in their self-monitored capillary blood glucose and insulin regimen. Sixty-one percent of women noted perimenstrual changes in capillary blood glucose. The commonest pattern was a premenstrual rise in glucose. Thirty-six percent of all study participants were making adjustments to their insulin dose in response to these changes in capillary blood glucose. There was no statistical difference in the mean glycated haemoglobin of subjects making perimenstrual adjustments in insulin (79.1 mmol mol-1 haem) compared to subjects who noted cyclical capillary glucose changes but did not adjust insulin (73.0 mmol mol-1 haem). Sixty-seven percent of subjects taking the fixed dose oestrogen/progesterone oral contraceptive pill (OCP) noted perimenstrual changes in glucose. In summary, a third of the women surveyed made perimenstrual adjustments to their insulin dose, but there was no evidence to suggest that this behaviour was associated with improved glycaemic control. Use of the fixed dose combined oral contraceptive pill did not eliminate perimenstrual changes in glucose.

Adolescent↗

PubMed1996

Development of a skin model based on insoluble fibrillar collagen.

A biocompatible, 3-dimensional, noncontracting, crosslinked collagen matrix was adapted to promote differentiation of epidermal keratinocytes. To produce the matrix, a 3% wt/wt dispersion of insoluble bovine collagen containing 5 mg polylysine/g collagen in 0.001 N HCl was blended, lyophilized, and crosslinked using a dehydrothermal technique. Matrices 4 cm2 and 3 mm thick were seeded with human dermal fibroblasts (1 x 10(5)/cm2). After 5 days in culture, the matrices were seeded with human epidermal keratinocytes (1 x 10(5)/cm2). The cultures were grown submerged for 1 week and raised to the liquid/air interface for 3 weeks to promote epidermal differentiation. Based on morphology and immunological staining with antibodies for human involucrin, keratin 1 (k1), filaggrin, and loricrin, the state of differentiation of the epidermal layer was nearly equivalent to that seen with cultures grown on contracted collagen lattices produced according to the methodology described in the literature and similar to the pattern produced in normal neonatal foreskin. These results demonstrate the usefulness of an in vitro skin model employing a crosslinked collagen matrix that permits the incorporation of additional covalently linked bioactive molecules during matrix formation.

Biocompatible Materials↗

PubMed1996

Islet cell antibodies and antibodies against glutamic acid decarboxylase in newly diagnosed adult-onset diabetes mellitus.

This study aimed to determine the prevalence of antibodies against glutamic acid decarboxylase (anti-GAD) and islet cell antibodies (ICA) in relation to beta-cell function in adults newly-diagnosed with diabetes mellitus. beta-cell function was assessed in adults aged 25-70 years newly-diagnosed with diabetes mellitus (n = 84) and control subjects (n = 34) using a 1.6 MJ mixed meal test procedure. beta-cell function was evaluated by the true insulin (defined as immunoreactive insulin minus proinsulin) response to the mixed meal test. Subjects were classified on the basis of the area under the true insulin curve (normal 16830-107700 pmol min/I) and the sum of the 30 and 60 min incremental response (normal 285-3295 pmol/I). The prevalence of anti-GAD and ICA was determined using radioimmunoprecipitation and indirect immunofluorescence, respectively. Twelve (14%) of the study cohort were insulin deficient showing little or no true insulin release. Of the insulin deficient individuals, seven (58%) subjects were anti-GAD antibody positive, compared with eleven (15%) of the subjects without insulin deficiency (P < 0.001). Seven (58%) insulin deficient subjects were ICA positive, whereas only two (3%) non-insulin deficient subjects were ICA positive (P < 0.001). Eight (67%) of the insulin deficient individuals had anti-GAD or ICA, compared with twelve (17%) of those who were not insulin deficient (P < 0.001). The positive predictive values for insulin deficiency of anti-GAD and ICA were 39 and 78% respectively. The sensitivity of both antibodies for detecting insulin deficiency was 50%. The specificity for detecting insulin deficiency was 85% for anti-GAD and 97% for ICA. Positivity for both anti-GAD and ICA gave a specificity and positive predictive value for insulin deficiency of 99%, and a sensitivity of 50%. Nearly one in seven adults presenting with diabetes mellitus as a new diagnosis are insulin deficient using our criteria. Loss of beta-cell function in two thirds of individuals who are insulin deficient can be identified by anti-GAD and ICA. Early detection of these immune markers of beta-cell damage creates the potential for immune modulation to limit such damage.

Adult↗

PubMed1996

Coronal caries in the primary and permanent dentition of children and adolescents 1-17 years of age: United States, 1988-1991.

The Third National Health and Nutrition Examination Survey-Phase 1, conducted from 1988 to 1991 in the United States, included an assessment of dental caries in US children and adolescents and provided the opportunity for differences in dental caries status to be viewed by a ge, sex, race, and race-ethnicity. The measurement of dental caries in children and adolescents from 2-17 years of age included the number of decayed, missing, and filled permanent tooth surfaces and teeth, and the number of decayed, and filled primary tooth surfaces and teeth. Additionally, a brief visual inspection for the presence or absence of early childhood caries in the maxillary incisors was conducted for children 12-23 months of age. The survey yielded weighted estimates for 1988-1991 for over 58 million US children and adolescents 1 to 17 years of age. For infants aged 12-23 months, 0.8% were scored positive for early childhood caries. Over 60% (62.1%) of the children aged 2-9 years were caries-free in their primary dentition. Over half (54.7%) of the children 5-17 years were caries-free in their permanent dentition. The occurrence of caries in the permanent dentition is clustered: A quarter of the children and adolescents ages 5 to 17 with at least one permanent tooth accounted for about 80% of the caries experienced in permanent teeth. Differences in caries experience were found among race and race-ethnicity subpopulations, and caries patterns for the primary and permanent dentition were dissimilar. Further analyses are needed to explore other potential determinants of caries in children.

Adolescent↗

PubMed1996

Coronal and root caries in the dentition of adults in the United States, 1988-1991.

Dental public health policy planning requires accurate and current information about the extent of caries in the United States population. These data are available from the caries examination from Phase 1 of the Third National Health and Nutrition Examination Survey, which found that 94% of adults in the United States show evidence of past or present coronal caries. Among the dentate, the mean number of decayed and filled coronal surfaces per person was 21.5. Dentate females had a lower number of untreated coronal tooth surfaces with caries (1.5), but a higher mean number of treated and untreated surfaces per person (22.7) than males, with scores of 2.1 and 20.2, respectively. Estimates for race-ethnicity groups were standarized by age and gender to control for population differences among them. Dentate non-Hispanic blacks (11.9) and Mexican-Americans (14.1) had half the number of decayed and filled coronal surfaces as non-Hispanic whites (24.3), but more untreated surfaces (non-Hispanic whites, 1.5; non-Hispanic blacks, 3.4; Mexican-Americans, 2.8). Mexican-Americans were most likely to be dentate, had the highest average number of teeth, and had 25% fewer decayed, missing, and filled coronal surfaces (37.6) than non-Hispanic blacks (49.2) and non-Hispanic whites (51.0). Root caries affected 22.5% of the dentate population. Blacks had the most treated and untreated root surfaces with caries (1.6), close to the value for Mexican-Americans (1.4). The score for non-Hispanic whites was 1.1. Untreated root caries is most common in dentate non-Hispanic blacks (1.5), followed by Mexican-Americans (1.2), with non-Hispanic whites (0.6) having the fewest untreated carious root surfaces. Race-ethnicity groups were disparate with respect to dental caries; effort is needed to treat active caries common in some population subgroups.

Adolescent↗

PubMed1996

Selected restoration and tooth conditions: United States, 1988-1991.

The DMF index provides one source of information on past and present dental caries experience; however, important limitations hinder its ability to characterize fully the impact of dental caries. The purpose of this paper is to describe a measure of selected restoration and tooth conditions that supplements information from the DMF index and to report on the application of this measure as part of the Third National Health and Nutrition Examination Survey, Phase 1, conducted between 1988 and 1991. Data from this survey were used to estimate the prevalence and severity of selected disaggregated physical and biological oral conditions among dentate adults aged 18 to 74 years. Trained, standardized, and calibrated dentist examiners assessed 28 permanent teeth or tooth spaces for each of 6,767 subjects. Teeth or tooth spaces were classified based on criteria for: defective intracoronal restorations, crowns, or bridges; gross loss of tooth structure associated with a restoration; pulpal involvement; or retained roots. Approximately 40.5%, or 61.6 million, dentate adults had at least one tooth or tooth space that met the criteria. Among all persons, an average of 0.9 teeth or tooth spaces met the criteria for at least one category. Adults with at least one scored tooth or tooth space had an average of 2.2 such teeth or tooth spaces. Data from this assessment supplement information available from the DMF index to provide a broader profile of the impact of dental caries on permanent teeth of US adults.

Adolescent↗

PubMed1996

Periodontal status in the United States, 1988-1991: prevalence, extent, and demographic variation.

This paper reports estimates of the periodontal status of US population derived from data from Phase 1 of the Third National Health and Nutrition Examination Survey conducted by the National Institute of Dental Research from 1988-1991. A total of 7,447 dentate individuals 13 years of age and older, representing approximately 160.3 million civilian non-institutionalized Americans, received a periodontal assessment. Measurements of gingival bleeding, gingival recession level, periodontal pocket depth, and calculus were made by dental examiners. Assessments were made at the mesiobuccal and mid-buccal sites of all fully erupted permanent teeth present in two randomly selected quadrants, one maxillary and one mandibular. All data were weighted and standard errors calculated by special software to adjust for the effect of sample design. Although over 90% of persons 13 years of age or older had experienced some clinical loss of attachment (LA), only 15% exhibited more severe destruction (LA > or = 5 mm). Prevalence of moderate and severe LA and gingival recession increased with age, while prevalence of pockets > or = 4 mm or > or = 6 mm did not. These data suggest that the increasing prevalence of LA with age is more associated with increasing prevalence of recession than with changes in the prevalence of pockets or age. The extent or number of affected sites with advanced conditions for loss of attachment, pocket depth, or recession was not large for any age group. Differences in prevalence of moderate and severe loss of attachment, moderate and deep pockets, and recession were found among gender and race-ethnicity groups. Females exhibited better periodontal health than males, and non-Hispanic whites exhibited better periodontal health than either non-Hispanic blacks or Mexican-Americans.

Adolescent↗

PubMed1996

Tooth retention and tooth loss in the permanent dentition of adults: United States, 1988-1991.

While the overall prevalence of tooth loss and edentulism has been declining in the United States over the past several decades, important variations remain among subgroups of the population. Data from Phase 1 of the Third National Health and Nutrition Examination Survey (NHANES III) provide the most current estimates of the prevalence and distribution of tooth retention and tooth loss in the United States. Weighted analyses were conducted for all adults 18+ years of age (n=8,366) and for selected age, gender, and race-ethnicity groups. In 1988-91, 89.5% of the population was dentate, and 30.5% had retained all 28 teeth. The mean number of teeth retained was 21.1 for all adults and 23.5 for dentate persons. The most commonly retained teeth in the mouth were the six anterior teeth in the lower arch. Conversely, 10.5% of the population was edentulous. Partial edentulism was much more common in the upper arch than in the lower arch. The most commonly missing teeth were the first and second molars. Age was strongly related to every measure of tooth retention and tooth loss. Gender was not related to any of these measures, after adjustment for age. Race-ethnicity was consistently related to these measures, after adjustment for age and gender. In general, Mexican-Americans had the lowest and black non-Hispanics the highest rates of tooth loss. Future research needs to examine a wide range of potential correlates of tooth retention and tooth loss before we can understand the complex interplay among the personal, dental, and environmental factors influencing tooth retention and tooth loss in the United States.

Adolescent↗

PubMed1996

Denture use and the technical quality of dental prostheses among persons 18-74 years of age: United States, 1988-1991.

For persons without all or some of their natural teeth in one or both arches, the use of a complete or partial denture and the quality of the denture used are important aspects of their oral health and functioning. This report of prosthodontic findings from the first three years of the 1988-94 National Health and Nutrition Examination Survey (NHANES III-Phase 1) provides estimates of denture use among the US civilian non-institutionalized population 18-74 years of age, as well as seminal information on the technical quality of dental prostheses nationwide. NHANES III-Phase 1 prosthodontic findings indicated that about one in five persons 18-74 years of age wears a removable prosthodontic appliance of some type. Overall, removable prosthodontic appliances are worn disproportionately more often by women than by men, and less frequently by whites than by blacks. Comparisons among race-ethnicity categories indicate that Mexican-Americans are less likely to use dentures than either of their non-Hispanic counterparts. Analyses of prosthodontic evaluation data indicated that approximately 60% of denture users have at least one problem with a denture. These findings from the oral component of NHANES III-Phase 1 provide clear indications that, despite increasing trends in tooth retention, dependence on removable prosthodontic appliances is still a reality of life for millions of Americans.

Adolescent↗

PubMed1996

Dental caries and sealant usage in U.S. children, 1988-1991: selected findings from the Third National Health and Nutrition Examination Survey.

This article provides estimates of dental caries and dental sealant use among U.S. children and adolescents, obtained from Phase 1 (1988-1991) of the Third National Health and Nutrition Examination Survey. More than 60 percent of children under the age of 10 years had a caries-free primary dentition; among children and adolescents aged 5 to 17 years, about 55 percent had a caries-free permanent dentition. The highest percentages of dental caries among children and adolescents continue to be distributed disproportionally among about 25 percent of the U.S. population. Fewer than one in five U.S. children and adolescents aged 5 to 17 years had one or more sealed permanent teeth.

Adolescent↗

PubMed1996

Dental caries, restoration and tooth conditions in U.S. adults, 1988-1991. Selected findings from the Third National Health and Nutrition Examination Survey.

This article provides estimates of dental caries experience and selected restorative and tooth conditions among U.S. adults, obtained from Phase 1 (1988-1991) of the Third National Health and Nutrition Examination Survey. Between 1988 and 1991, 94 percent of adults in the United States showed evidence of past or present coronal caries. Based on the data collected, the authors estimate that about 40.5 percent, or 61.6 million, dentate adults had at least one tooth or tooth space that could potentially benefit from professional treatment. Minimally, it is estimated that 135.6 million tooth or tooth spaces among U.S. adults may benefit from professional treatment. These estimates supplement information available from the DMF index to provide a broader profile of the impact of dental caries on permanent tooth of U.S. adults.

Adolescent↗

PubMed1996

Gingival state and dental calculus in early-onset periodontitis.

This study was undertaken to 1) compare the prevalence of gingival inflammation and dental calculus in adolescents with early-onset periodontitis and their matched controls and 2) assess and compare the relationship between the presence of dental calculus and the extent of gingival bleeding and attachment loss in these subjects. The study group consisted of 1,285 13 to 20 year-old individuals, 651 males and 634 females, selected from a national survey of the oral health of U.S. adolescents in 1986/1987. It included 709 (55.2%) Blacks, 224 (17.4%) Hispanics, and 352 (27.4%) Whites. Eighty-nine subjects had localized or generalized juvenile periodontitis (JP), 218 had incidental attachment loss (IAL), and 978 were without clinical attachment loss (controls). The controls were matched to cases on gender, race, age, and geographic location. The subjects were examined clinically to assess the percentage of sites with gingival bleeding and supragingival calculus only and subgingival calculus with or without supragingival calculus. The IAL and JP groups had significantly more gingival bleeding and subgingival calculus than the controls. Also, the JP group had significantly higher prevalence of both conditions than the IAL group. The percentage of sites with supragingival calculus was not different between the groups, but varied by ethnicity. Hispanics with JP had the highest percentage of sites with gingival bleeding and subgingival calculus, and the lowest percentage of sites with only supragingival calculus. The results demonstrate that gingival inflammation and subgingival calculus are associated with early periodontal breakdown, and contradict earlier reports of early-onset periodontitis not being associated with these factors.

Adolescent↗

PubMed1996

Dental caries and tooth loss in adolescents with early-onset periodontitis.

The aim of this study was to assess the caries experience and tooth loss over 6 years in subjects with early-onset periodontitis as compared to their matched controls, and to describe the characteristics of teeth lost during this period. A multi-stage probability sample representing 8th to 12th grade U.S. schoolchildren were screened during the 1986/1987 school year to identify subjects with early-onset periodontitis (cases). The examination included measuring the clinical attachment level, presence of caries and dental restorations, and tooth loss. A random sample of controls without early-onset periodontitis were selected for a follow-up examination and were matched to cases on gender, race, age, and geographic location. A total of 266 subjects, with a mean age of 16 years at baseline, were examined during the 1992/1993 school year and were classified into localized (LJP) and generalized juvenile periodontitis (GJP), incidental attachment loss (IAL), and control groups. Whites had more caries experience than Blacks and Hispanics, but there were no significant differences in tooth loss between the ethnic groups. The LJP and the IAL groups, respectively, had higher and lower overall caries experience than the control group. The LJP group had a significantly higher number of missing teeth at follow-up, and exhibited more extensive tooth mortality during 6 years than the control group. The GJP group also showed more tooth loss than the control group, but the difference was not statistically significant. In the LJP, GJP, IAL, and control groups, respectively, 43%, 32%, 26%, and 18% of the subjects lost teeth over 6 years due to disease. The findings showed differences in caries activity between the early-onset periodontitis groups and a variation by race. The findings suggest that loss of periodontal support was the principal cause for tooth loss in the LJP and GJP groups, and that dental caries was the principal cause for tooth extraction in the IAL and the control groups.

Adolescent↗

PubMed1996

Early-onset periodontitis: progression of attachment loss during 6 years.

We studied the pattern of progression of early-onset periodontitis and the change in the extent and severity of the periodontal condition in adolescents who were followed for 6 years. In a national survey of the oral health of U.S. children, 14,013 adolescents were examined clinically in 1986/1987 to assess the periodontal attachment loss of teeth. Individuals with early-onset periodontitis within this population were identified and classified into localized juvenile periodontitis (LJP), generalized juvenile periodontitis (GJP), and incidental attachment loss (IAL) groups. Ninety-one subjects, 13 to 20 years old at baseline, were examined 6 years later. They included 51 males and 40 females; and 72 Blacks, 6 Hispanics, and 13 Whites. They were clinically re-examined and then reclassified according to their periodontal status at follow-up. The severity and extent of these diseases continued to increase during the study period. In teeth that were affected at baseline, the lesions had progressed to include deeper portions of the periodontium, and more of the teeth unaffected at baseline exhibited periodontal attachment loss at follow-up, thus changing the disease characteristics and the basis for the clinical classification. Of the individuals classified with LJP at baseline, 62% continued to have LJP 6 years later and 35% developed GJP. Of those classified with GJP initially, all but two (82%) continued to have GJP at follow-up. Among the IAL group, 28% of subjects developed LJP or GJP, and 30% were reclassified in the no attachment loss group. Molars and incisors were the teeth most often affected in all three groups. The mean change in attachment loss over 6 years in the LJP, GJP, and IAL groups was 0.45, 1.12, and 0.13 mm, respectively. The present findings demonstrate the limitations of the currently used morphological criteria in the classification of early-onset periodontitis. The findings also suggest that the difference between LJP and GJP is in the number and type of teeth involved, and that the two classifications progress similarly, with some cases of LJP developing into GJP.

Adolescent↗

PubMed1996

Mitochondrial FAD-glycerophosphate dehydrogenase and G-protein-coupled inwardly rectifying K+ channel: No evidence for linkage in maturity-onset diabetes of the young or NIDDM.

Two genes that have potentially important regulatory roles in insulin secretion are both located on chromosome 2q24.1. G-protein-coupled muscarinic potassium channel (GIRK1) is an inwardly rectifying K+ channel that helps to maintain the resting potential and excitability of cells. Mitochondrial FAD-linked glycerophosphate dehydrogenase (m-GDH) catalyzes a rate-limiting step of the glycerol phosphate shuttle in pancreatic islets. Reduced m-GDH activity has been demonstrated in islets isolated from diabetic subjects compared with islets from nondiabetic control subjects and from the diabetic GK rat. To study the relationship between these candidate genes and NIDDM, we have examined a simple tandem-repeat polymorphism (STRP) close to both the KCN J3 (GIRK1) locus and the m-GDH locus. In a linkage study of three maturity-onset diabetes of the young (MODY) pedigrees, not linked to MODY1, MODY2, or MODY3, a cumulative score of - 9.6 at a recombination fraction of theta = 0 excluded linkage. In a population-association study, no linkage disequilibrium for the STRP was found between 190 unselected NIDDM patients and 60 geographically and age-matched white nondiabetic subjects (chi2 = 1.51 on 3 df, P = 0.68). Thus, mutations involving the genes for GIRK1 or FAD-glycerophosphate dehydrogenase are unlikely to cause MODY, and a common mutation in either gene is unlikely to contribute to NIDDM in whites. These data do not exclude mutations in some families or other ethnic groups.

Animals↗