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PubMed1991

Immune material processing by phagocyte cell system in cryoglobulinemia.

An impaired function of splenic macrophages, measured as the clearance rate of erythrocytes coated with IgG (E-IgG), was observed in 7 out of 8 cryoglobulinemic patients with severe urinary abnormalities and systemic symptoms, and in 0 out of 6 patients without urinary symptoms and only mild systemic signs of disease. The E-IgG clearance rate was not related to HLA or Rh phenotype, patients' age or disease duration. Moreover, longitudinal studies showed this parameter to be strictly related to disease activity. To investigate the nature of the defect, five series of analyses were planned using peripheral blood phagocytes (PBP) from 8 patients: a) detection of cell-bound immune material by using the antibody CE59 directed to the Fc fragment of IgG modified by the antibody-antigen reaction; b) cytofluorometric and/or radiometric analyses of the cell surface expression of HLA II, CR1 and FcR structures by means of specific monoclonal antibodies (MoAbs); c) electron microscopy (EM) examination of diverse combinations of cryoglobulins incubated with PBP from patients and normals; d) analysis of cryoglobulin-induced inhibition of E-IgG phagocytosis; e) measurement of the generation of chemiluminescence (CL) in response to Zymosan, Phorbol Myristate Acetate and n-Formyl-Methyonine-Leucine-Phenilalanine (n-FMLP). Patients' PBP were found to have a higher amount of cell-bound immune material as compared to normals (p less than 0.01). CR1 and FcR expression was not different from controls, whereas a slight increase in percentage of monocytes bearing HLA II structures was found in patients (p less than 0.05). Upon EM examination no obvious differences were found in the internalization capacity of cryoglobulins between patients and controls. The CL production was lower than normal (p less than 0.02), whatever stimulus used, with a maximal impairment for n-FLMP (p less than 0.005), the most specific test probe for cytoskeleton integrity. Finally, a remarkable cryoglobulin-induced inhibition of E-IgG phagocytosis was shown. A combination of saturation mechanisms and intracellular abnormalities could underlie the apparent discrepancy between E-IgG clearance defect and preserved potential of cryoglobulin internalization in cryoglobulinemia.

Adult↗

PubMed2005

Heterozygote effects in mice with partial truncations in the growth hormone receptor cytoplasmic domain: assessment of growth parameters and phenotype.

The GH receptor (GHR) is essential for normal postnatal growth and development, and the molecular basis of GHR action has been studied intensively. Clinical case studies and more recently mouse models have revealed the extensive phenotype of impaired GH action. We recently reported two new mouse models, possessing cytoplasmic truncations at position 569 (plus Y539/545-F) and 391, which were created to identify functional subdomains within the cytoplasmic signaling domain. In the homozygous state, these animals show progressively impaired postnatal growth coupled with complex changes in gene expression. We describe here an extended phenotype analysis encompassing the heterozygote state to identify whether single copies of these mutant receptors bring about partial or dominant-negative phenotypes. It appears that the retention of the ubiquitin-dependent endocytosis motif in the N-terminal cytoplasmic domain permits turnover of these mutant receptors because no dominant-negative phenotype is seen. Nonetheless, we do observe partial impairment of postnatal growth in heterozygotes supporting limited haploinsufficiency. Reproductive function is impaired in these models in a progressive manner, in parallel with loss of signal transducer and activator of transcription-5 activation ability. In summary, we describe a more comprehensive phenotypic analysis of these mouse models, encompassing overall and longitudinal body growth, reproductive function, and hormonal status in both the heterozygote and homozygote state. Our results suggest that patients expressing single copies of similarly mutated GHRs would not display an obvious clinical phenotype.

Animals↗

PubMed1996

Resistance to (-)-2',3'-dideoxy-3'-thiacytidine (3TC) in HIV-1 isolated from paediatric patients.

We conducted detailed virological evaluations of 16 HIV-1-infected paediatric patients treated with 3TC (lamivudine) monotherapy. High-level phenotypic resistance against this compound (up to 2,500-fold) was seen in virtually all cases, usually within 8-12 weeks of initiation of therapy. This was concomitant with the appearance of the M184V mutation in viral reverse transcriptase, previously shown to be responsiblefor such resistance. Viral burden fell in virtually all cases after commencement of therapy, and remained below baseline in each instance studied, despite a rebound effect and the appearance of drug resistance. Viral isolates from some patients underwent a switch from a non-syncytium-inducing (NSI) to a syncytium-inducing (SI) phenotype during the course of the study, although no relationship was apparent between dose of drug employed, time to development of drug resistance or time of appearance of SI phenotype.

Anti-HIV Agents↗

PubMed1995

Positron emission tomography in familial Alzheimer disease.

There is increasing evidence for genetic heterogeneity in Alzheimer disease. A longitudinal clinical and imaging study had been established in order to determine whether specific phenotypic profiles are present in aetiologically distinct familial Alzheimer disease (FAD) pedigrees. [18F]fluorodeoxyglucose positron emission tomography has been used in conjunction with statistical parametric mapping to determine the relative distribution of hypometabolism. A parietotemporal deficit has been observed in individuals from both amyloid precursor protein mutation and chromosome 14 linked FAD families. Preliminary data from asymptomatic individuals at risk of FAD shows similar, although a less extensive pattern of deficit.

Aged↗

PubMed1998

Effects of quantitative trait loci for lipid phenotypes in the rat are influenced by age.

1. Previous study on the backcross hybrids derived from a cross of the spontaneously hypertensive rat (SHR/Mol) and the spontaneously diabetic BB/OK rat demonstrated the existence of quantitative trait loci (QTL) affecting lipid phenotypes on chromosome 4 and suggestive linkage of lipid phenotypes with markers on chromosome 1. Because the previous study was performed with backcross hybrids at 12 weeks of age and it is known that lipid phenotypes can show age-related differences, in the present study, the effect of QTL (chromosome 1 and 4) on serum triglycerides and cholesterol was longitudinally analysed between 20 and 32 weeks of age in backcross hybrids. 2. The results of the present study show that the effect of QTL on chromosome 4 (between It-6 and D4Mit9) for serum triglycerides was maximal at 20 weeks of age, but disappeared at 32 weeks of age. In contrast, the effect of QTL on serum total cholesterol on chromosome 4 (Npy-Spr) was maximal at 32 weeks of age. In contrast with the first study (12 weeks), the longitudinal investigation showed significant linkage of DIMit14 marker with lipid phenotypes on chromosome 1. 3. The results of the present study indicate the necessity of considering the role of age in QTL analysis of lipid phenotypes.

Aging↗

PubMed2026

Dynamics of gut bacteriophage in diversity outbred mice studied over lifespan and during extreme caloric restriction.

BACKGROUND: The majority of bacteria in the vertebrate gut harbor integrated bacterial viruses ("bacteriophages" or "phages"; integrated phage are termed "prophages"). To probe phage replication strategies in the mammalian gut microbiome, we investigated phage activity in a large longitudinal study of diversity outbred mice (913 animals) undergoing extreme dietary restriction with detailed phenotypic characterization across lifespan. RESULTS: We assembled 54,119 candidate DNA viral genomes from 2997 longitudinal metagenomes, forming 6462 viral operational taxonomic units (vOTUs). Over 85% of vOTUs annotated as novel. Viruses annotated predominantly as prophages in the Caudoviricetes class. We detected no eukaryotic DNA viruses, and none of the strictly lytic Crassvirales order that is abundant in human gut. The most prevalent phages had the widest predicted host ranges. The relative abundance of most phages was highly correlated to that of their inferred host bacteria, suggesting quiescent prophages dominate viral metagenomes, consistent with "piggyback-the-winner" dynamics. After accounting for close phage-bacterial covariation, we did identify a subset of phages changing in relative abundance and prevalence relative to their hosts in response to dietary restriction and aging. In particular, phages with larger genomes become less common in diets with restricted calories, potentially reflecting a higher fitness cost to their host. Generalist phages were enriched for a gene encoding a single-strand DNA binding protein which is reportedly involved in DNA repair and protection from nucleases encoded by host cells. Lytic phages became more common with aging, and we observed a reduction in phage richness with age, both findings previously observed in human cohorts. CONCLUSION: These studies enrich our understanding of DNA phage dynamics in gut while emphasizing the predominance of "piggyback-the-winner" strategies.

Animals↗

PubMed2003

Nonparametric longitudinal allele-sharing model.

Basically no methods are available for the analysis of quantitative traits in longitudinal genetic epidemiological studies. We introduce a nonparametric factorial design for longitudinal data on independent sib pairs, modelling the phenotypic quadratic differences as the dependent variable. Factors are the number of alleles shared identically by descent (IBD) and the age categories at which the dependent variable is measured, allowing for dependence due to age. To identify a linked marker a rank statistic tests the influence of IBD group on phenotypic quadratic differences. No assumptions are made on normality or variances of the dependent variable. We apply our method to 71 sib pairs from the Framingham Heart Study data provided at the Genetic Analysis Workshop 13. For all 15 available markers on chromosome 17 we analyzed the influence on systolic blood pressure. In addition, different selection strategies to sample from the whole data are discussed.

Adult↗

PubMed2003

Expression profiling identifies responder and non-responder phenotypes to interferon-beta in multiple sclerosis.

Autoimmune diseases such as multiple sclerosis are characterized by complex genetic traits and pathomechanisms that translate into clinical heterogeneity. This wide heterogeneity of multiple sclerosis as well as different biological responses to immunomodulatory drugs can be expected to contribute to differential treatment responses. Strategies that dissect the relationship between the treatment response and the biological characteristics in individual patients are valuable not only as a clinical tool, but also in leading to a better understanding of the disease. Here we address the in vitro and ex vivo RNA expression profile under one approved therapy of multiple sclerosis, interferon-beta (IFN-beta, Betaseron), by cDNA microarrays and demonstrate that non-responder and responder phenotypes to IFN-beta as assessed by longitudinal gadolinium-enhanced MRI scans and clinical disease activity differ in their ex vivo gene expression profile. These findings will help to better elucidate the mechanism of action of IFN-beta in relation to different disease patterns and eventually lead to optimized therapy.

Follow-Up Studies↗

PubMed1998

The apolipoprotein E phenotype has a strong influence on tracking of serum cholesterol and lipoprotein levels in children: a follow-up study from birth to the age of 11 years.

The extent to which an individual maintains his position relative to the rest of the population is called tracking. The objective of this study was to examine the effect of the apolipoprotein E (apoE) phenotype on the tracking of serum cholesterol and lipoproteins from birth to the age of 11 y. In a longitudinal follow-up study of healthy children, concentrations of total serum cholesterol and triglyceride were determined at birth (n = 193), and at the ages of 2 (n = 192), 4 (n = 192), 6 (n = 190), 9 (n = 188), and 12 mo (n = 196), and 5 (n = 162) and 11 y (n = 153). Concentrations of total HDL, HDL2, and HDL3, VLDL, and LDL cholesterol were determined at 2, 6, 9, and 12 mo (n = 36), and 5 (n = 162) and 11 y (n = 153). The apoE phenotype was determined in 151 children. The children had the following apoE phenotypes: 4 had type 4/4 and 40 type 3/4 (group apoE4), 94 had type 3/3 (group apoE3), and 11 had type 2/3 and 2 type 2/4 (group apoE2). The correlation coefficients for total cholesterol levels during childhood compared with the level at 11 y of age were: 0.03 at birth, 0.26 (p < 0.001) at 2 mo, 0.24 (p < 0.001) at 4 mo, 0.24 (p < 0.001) at 6 mo, 0.28 (p < 0.001) at 9 mo, 0.41 (p < 0.001) at 12 mo, and 0.60 (p < 0.001) at 5 y. When the children were divided into three groups according to their apoE phenotypes, these three groups had the following correlation coefficients at 4 mo, 12 mo, or 5 y of age compared with the level at the age of 11 y; group apoE2: r = 0.65 (p < 0.01), r = 0.59 (p < 0.01), and r = 0.72 (p < 0.01); group apoE3: r = 0.27 (p < 0.01), 0.43 (p < 0.001), and r = 0.64 (p < 0.001); and group apoE4: r = 0.14 (p = NS), r = 0.33 (p < 0.05), and 0.42 (p < 0.01). The apoE phenotype also strongly influenced the tracking of the LDL cholesterol levels; the correlation coefficients between 5 and 11 y of age were for group apoE2 r = 0.84 (p < 0.001), for group apoE3 r = 0.70 (p < 0.001), and for group apoE4 r = 0.37 (p < 0.05). Our results indicate that the apoE phenotype strongly influences the tracking of lipids. The children having apoE 2/3, 2/4, and 3/3 phenotypes maintained their relative cholesterol and lipoprotein levels better than the others throughout the first 11 y of age. Because the apoE phenotype strongly affects the tracking of serum cholesterol, the usefulness of cholesterol screening in predicting future cholesterol values should be analyzed, keeping the apoE phenotype in mind.

Apolipoproteins E↗

PubMed2000

Prevalence of HIV-1 resistant to antiretroviral drugs in 81 individuals newly infected by sexual contact or injecting drug use. Investigators of the Quebec Primary Infection Study.

OBJECTIVE: Prolonged treatment with antiretroviral drugs results in the selection of HIV-1 variants with mutations conferring resistance to nucleoside and non-nucleoside reverse transcriptase inhibitors (NRTI and NNRTI) or to protease inhibitors (PI). There is serious concern about transmission of resistant viruses to newly infected persons. This study monitored the prevalence of resistant viruses in individuals undergoing primary HIV infection. DESIGN: Resistance testing was performed on 81 individuals infected between 1997 and 1999 by injecting drug use (n =21), sexual (n = 56), or unknown (n = 4) transmission. METHODS: Automated sequencing was used to genotype the reverse transcriptase (RT) and protease regions of virus isolated from patients' plasma. The phenotypic susceptibility of stimulated peripheral blood mononuclear cells to antiretroviral drugs was assayed. Line probe assays detected quasispecies variations in wild-type and mutated RT codons. RESULTS: A high prevalence of PI and RT genotypic variants, associated with high-level resistance to antiretroviral drugs, was observed in individuals newly infected by injecting drug use (PI = 24%, RT = 24%) or sexual transmission (PI = 12%, RT = 22%). The PI mutations, L101, V82A, and L90M, were found in 10.5, 3 and 4% of cases, respectively; whereas for RT, primary mutations at positions T215Y (zidovudine), M184V (lamivudine), T69D/A (zalcitabine), and K103N (multi-NNRTI) were present in 8, 5, 4, and 4% of subjects, respectively. Resistance to NRTI was demonstrated by phenotypic, genotypic, and line probe analyses. Transmission of multidrug (NRTI/NNRTI/PI) resistance in eight subjects (9.9%) was confirmed by showing that source partners possessed viruses of similar genotype. CONCLUSIONS: The transmission of drug-resistant HIV is a serious problem that merits further attention by public health officials as well as virologists and clinicians.

Anti-HIV Agents↗

PubMed2003

Molecular epidemiology of asymptomatic bacteriuria in the elderly.

OBJECTIVES: to determine the incidence and the dynamics of asymptomatic bacteriuria in ambulatory nursing home residents, and to characterise bacteria according to their phenotype and genotype. DESIGN: an 18 months prospective longitudinal study. SUBJECTS: 42 nursing home residents (31 female, 11 males) without indwelling catheters. METHODS: urine was sampled every 3 months. Antibiograms, biotyping and ribotyping were performed. RESULTS: the cumulative percent of infection for females and males was 75% and 27% respectively. Osteoporosis was associated with bacteriuria. Ribotypes of consecutive Escherichia coli isolates indicated that each patient harboured a different strain. CONCLUSIONS: asymptomatic bacteriuria in the elderly is a dynamic and transient phenomenon. Osteoporosis is common among this population. Ribotyping is a powerful tool in the elucidation of the epidemiology of this bacteriuria.

Aged↗

PubMed1993

Immuno-effector characteristics of peritoneal cells during CAPD treatment: a longitudinal study.

Peritoneal cells (PC) from 75 patients were immuno-phenotypically and functionally characterized during the first year of CAPD treatment (PCcapd) and compared to PC obtained by laparoscopy of healthy women (control peritoneal cells). Patients were divided, according to their peritonitis incidence (PI), into a high PI (HPI) and a low PI group (LPI). The yield of PCcapd decreased significantly over the year. The differential cell count and immunophenotype of PCcapd remained unchanged in the LPI group, but the percentage of macrophages decreased over the year in the HPI group. Macrophages in the PCcapd, when compared to control peritoneal cells, had a less mature phenotype as measured by RFD7 expression but a higher Fc-receptor expression. The PCcapd showed a higher percentage of B cells, CD4 positive T cells and activated T cells bearing HLA-DR/DQ when compared to the control peritoneal cells. Over the year a decrease in chemotactic activity of the PCcapd towards 10(-8) M N-formylmethionyl-leucyl-phenylalanine and dialysis effluent was observed in LPI patients but not in HPI patients. After one year of treatment, a significantly higher percentage of phagocytosing macrophages in the PCcapd of HPI patients was found when compared to LPI patients. During the year there was an increase of immunophagocytosis of PCcapd independent of PI. In conclusion, the CAPD peritoneal cellular immune system showed signs of both immaturity and activation. The decrease in the yield and in the chemotactic activity of PCcapd suggests an adaptation to the chronic stimulus of the dialysis fluid.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed2000

A study of desmoglein 1 autoantibodies in pemphigus vulgaris: racial differences in frequency and the association with a more severe phenotype.

BACKGROUND: Pemphigus vulgaris (PV) is characterized by pathogenic autoantibodies to desmoglein (Dsg) 3, but additional antibodies to Dsg1, the pemphigus foliaceus antigen, are detectable in some cases. OBJECTIVES: To investigate the clinical significance of the presence of both Dsg 1 and 3 antibodies. METHODS: In 79 subjects with PV, enzyme-linked immunosorbent assays were used to detect IgG autoantibodies reactive with the ectodomain of Dsg1 and Dsg3. RESULTS: There was a clear association between the clinical phenotype and the Dsg antibody profile. All subjects had Dsg3 autoantibodies and 61% had coexisting Dsg1 antibodies (Dsg3+/Dsg1+). PV limited entirely to the mucosal surfaces was seen only in Dsg3+/Dsg1- patients, while additional Dsg1 antibodies (Dsg3+/Dsg1+) predicted cutaneous in addition to mucosal involvement. Although minor cutaneous involvement was observed in most Dsg3+/Dsg1- patients, severe cutaneous involvement was seen only in Dsg3+/Dsg1+ patients. Dsg1 antibodies were detectable early in the course of disease and their appearance did not relate to the use of systemic therapy. The proportion of Dsg1+ patients was higher in those of Indian origin compared with white northern Europeans (P < 0.05). CONCLUSIONS: These data suggest that the presence of Dsg1 antibodies is predictive of a potentially more severe disease and that genetic factors may determine the Dsg antibody profile.

Autoantibodies↗

PubMed2000

Transient T cell receptor beta-chain variable region-specific expansions of CD4+ and CD8+ T cells during the early phase of pediatric human immunodeficiency virus infection: characterization of expanded cell populations by T cell receptor phenotyping.

T cell receptor (TCR) repertoire perturbations are commonly detected in CD8+ T cells during adult primary human immunodeficiency virus (HIV) infection and have been associated with HIV-specific cytotoxic T cell responses. By use of flow cytometry, transient high-level TCR beta-chain variable region-specific expansions of CD4+ and CD8+ T cells were observed more frequently in HIV-infected children than in children exposed to HIV who remained uninfected. TCR beta-chain diversity analysis and diversity-specific polymerase chain reaction were used to study the clonality of expanded CD4+ and CD8+ subsets. In CD8+ T cells, structural features of the complement-determining regions 3 were altered during the course of the expansion, and persistent TCR clonotypes were observed, consistent with antigen-driven selection. In contrast, TCR beta-chain variable region-specific expansions without clonotypic overrepresentation or persistence were observed in CD4+ T cells, possibly related to HIV-specific helper T cell responses or to the progressive destruction of the CD4+ cell compartment.

CD4-Positive T-Lymphocytes↗

PubMed2000

Age-dependent changes in phenotypes and candidate gene analysis in a polygenic animal model of Type II diabetes mellitus; NSY mouse.

AIMS/HYPOTHESIS: The Nagoya-Shibata-Yasuda (NSY) mouse closely mimics human Type II (non-insulin-dependent) diabetes mellitus in that the onset is age-dependent, the animals are not severely obese, and both insulin resistance and impaired insulin response to glucose contribute to disease development. The aim of this study was to clarify the influence of age on the pathogenesis of diabetes and to analyse a candidate gene for Type II diabetes in this strain. METHODS: Several phenotypic characteristics related to diabetes mellitus were monitored longitudinally in male NSY and control C3H/He mice. The nucleotide sequence of Glut4, a candidate gene for Nidd1nsy (a susceptibility gene for Type II diabetes) on Chromosome 11, encoding insulin-sensitive glucose transporter, was determined in NSY and C3H mice. RESULTS: Glucose intolerance worsened with age, and fasting blood glucose and fasting plasma insulin concentration increased with age in NSY mice. Pancreatic insulin content increased until 24 weeks of age but then decreased at 48 weeks of age in NSY mice. The hypoglycaemic response to insulin was statistically significantly smaller in NSY than in C3H/He mice. The nucleotide sequence of GLUT4 cDNA was identical in NSY and C3H/He mice, but both were different from the sequence reported previously. CONCLUSION/INTERPRETATION: Insulin secretion and insulin resistance, as well as ageing possibly play an important part in the disease development in NSY mice. A decline of pancreatic insulin content in older age might cause the relative insulin deficiency in this strain. Nucleotide sequencing suggests that Glut4 is unlikely to be a candidate gene for Nidd1nsy.

3T3 Cells↗

PubMed2001

Stability of adiposity phenotypes from childhood and adolescence into young adulthood with contribution of parental measures.

OBJECTIVE: The stability of several indicators of body composition and adipose tissue distribution over 12 years was quantified. RESEARCH METHODS AND PROCEDURES: The participants were 77 boys and 76 girls who were evaluated along with their parents at baseline as children and adolescents (8 to 18 years of age) and remeasured as young adults 12 years later. Indicators of body composition included the body mass index, fat mass, fat free mass, percentage of body fat, sum of six skinfolds (SF6), and the first principal component of six age-adjusted skinfold residuals. Relative adipose tissue distribution was represented by the second principal component of skinfold residuals and a trunk-to-extremity skinfold ratio, adjusted for SF6. RESULTS: Partial interage correlations, controlling for initial age and length of follow-up, were 0.65 and 0.59 for the body mass index, 0.59 and 0.64 for fat mass, 0.65 and 0.57 for fat free mass, 0.50 and 0.57 for percentage of body fat, 0.66 and 0.44 for SF6, 0.64 and 0.42 for the first principal component of six age-adjusted skinfold residuals, 0.19 and 0.31 for the second principal component of skinfold residuals, and 0.41 and 0.47 for trunk-to-extremity skinfold ratio, adjusted for SF6, in men and women, respectively. Multiple regression analyses indicated that the significant partial R(2) values of parental measurements on the prediction of their offspring in young adulthood ranged from 2% to 9%. DISCUSSION: The results indicate moderately high stability of indicators of body composition and somewhat lower stability of measures of adipose tissue distribution. Overall, parental measures offer less predictive value than do measures of childhood and adolescent body composition and adipose tissue distribution.

Adipose Tissue↗

PubMed2004

Haptoglobin phenotype as a predictive factor of mortality in diabetic haemodialysis patients.

INTRODUCTION: The mortality rate in diabetic dialysis patients (DDPs) is over 15% per year, with the cause of death most often attributed to cardiovascular disease (CVD) or bacterial infection (sepsis). Identification of genetic markers predictive of early mortality would be useful in the evaluation of therapies for the reduction of mortality rate in this population. Haptoglobin (Hp) is a polymorphic protein which appears to confer differential susceptibility to bacterial infection and CVD. We therefore proposed that Hp phenotype can predict mortality in DDPs. METHODS: We tested this hypothesis prospectively in a longitudinal study of 392 dialysis patients from eight medical centres in Israel. Hp was determined by polyacrylamide gel electrophoresis. Patients were followed for all-cause mortality over a 3-year period. RESULTS: We found that Hp phenotype was a significant predictor of mortality in DDPs stratified by age. In diabetic individuals over 60 years of age there was a decrease in mortality associated with the Hp 1-1 phenotype (P = 0.03). However, in younger DDPs the Hp 2-2 phenotype was associated with a decreased mortality rate (P = 0.003). CONCLUSION: Hp phenotype may be useful in the risk stratification algorithm and management of DDPs.

Aged↗

PubMed1997

Gingival phenotypes in young male adults.

In a previous study on 42 young adult, periodontally healthy subjects without any attrition, abrasion or crown restoration, gingival thickness (GTH) was determined at facial aspects of premolars, canines and incisors by a novel ultrasonic device. GTH strongly depended on periodontal probing depth, width of gingiva (WG), and tooth type. Whereas the ratio of crown width to its length (CW/CL) was not identified as an explanatory variable, a significant influence of the subject was ascertained. The aim of the present study was to extend these analyses in order to identify subjects with different morphological characteristics of gingiva, i.e., gingival phenotypes. When employing cluster analysis on standardized parameters mean GTH, WG and CW/CL of upper canines, lateral and central incisors, 3 clusters were identified. Cluster A comprised 2/3 of subjects, displaying "normal" GTH, WG and CW/CL. Cluster B (n = 9, 21%) had a significantly thicker and wider gingiva, and a more quadratic form of upper front teeth. A 3rd cluster (cluster C, n = 5, 12%) was identified showing "normal" GTH, high CW/CL, but a narrow zone of keratinized tissue. Some characteristics of gingival phenotype of the upper front tooth region were also found at upper premolars (WG, CW/CL) but in general not at mandibular teeth. Present results clearly indicate evidence for the existence of different gingival phenotypes. Clinical relevance of these observations has to be tested in longitudinal studies.

Adult↗