Analysis of the association of IL4 polymorphisms with orthodontic mini-implant loss.

The aim of this study was to investigate the association of clinical characteristics and IL4 tag single nucleotide polymorphisms (SNPs; rs2227284 and rs2243268) with orthodontic mini-implant (MI) failure. The sample included 135 subjects of both sexes, mean age 48.7±10years (range 20-76years): 104 in the control group (patients without any MI loss) and 31 in the study group (patients presenting ≥1 MI loss). Genotypes were determined by real-time PCR. Bivariate and multivariate analyses were performed (P<0.05). No association was found between the selected tag SNPs and MI loss. The C allele of the IL4 rs2243268 polymorphism in the recessive model was more frequent in patients who had fewer MIs installed (≤2 vs. >2; P=0.043, odds ratio 0.65, 95% confidence interval 0.58-0.74). On multivariate analysis, smoking habit was significantly associated with the group with multiple MIs installed (P=0.036), however the significance of the association with rs2243268 was not maintained. No association was found between the socio-demographic, smoking, or genetic factors studied and MI loss. This study supports the interaction between host and environmental factors and its influence on susceptibility to orthodontic MI failure.

Estrogen receptor gene is associated with dental fluorosis in Brazilian children.

OBJECTIVES: The aim of this study was investigate the association between genetic polymorphisms in ESR1, ESR2, and ESRRB and dental fluorosis (DF) in a well-characterized sample of children from Curitiba, Brazil. MATERIAL AND METHODS: From a representative sample of 538 children, 12-year-old were evaluated. DF was assessed in erupted permanent teeth by the Dean's index modified. Fourteen polymorphisms were selected in intronic and intergenic regions of ESR1, ESR2, and ESRRB and genotyped in genomic DNA source from saliva using TaqMan chemistry and end-point analysis. Allele and genotype distributions between DF and DF free groups were analyzed using the Epi Info 7.2. Chi-square or Fisher's exact tests at a level of significance of 5% and odds ratios calculations with 95% confidence intervals were used to determine the statistical associations. RESULTS: Among 538 children, 147 were DF and 391 were DF free. Genotype distribution for the polymorphism rs12154178 in ESR1 was different between the two groups (p = 0.037; OR = 0.91; CI = 0.67-1.22). The dominant model analysis (AA+AC vs. CC) demonstrated that CC is a protective factor for DF (p = 0.038; OR = 0.51, 0.27-0.97 95% CI). We did not find differences in frequency distributions in the other evaluated polymorphisms. CONCLUSION: This study provides evidence that ESR1 is associated with DF. CLINICAL RELEVANCE: Dental fluorosis is an important condition that affects the mineralized tissues of the teeth. In severe cases, the treatment takes time and is extremely costly. This research provides evidences that there are genetic factors involved in dental fluorosis and will help professionals to plan more precise strategies to reduce dental fluorosis occurrence.

Analysis of the association of clinical factors and IL4 gene polymorphisms with root resorption in avulsed teeth after 1 year of replantation.

AIM: To investigate the association of clinical variables and polymorphisms (tag SNPs) in the interleukin 4 (IL4) gene, with the prognosis of avulsed and replanted teeth. METHODOLOGY: Ninety-four patients who suffered avulsion and had their teeth replanted and endodontically treated were included. Periapical radiographs were obtained soon after tooth replantation and after 1 year. For genotypic IL4 gene analysis, the DNA from oral mucosa cells was collected, and polymorphisms were investigated by real-time PCR. Univariate and multivariate analyses were performed to verify the association of clinical and genetic variables and the outcome of the replanted teeth (P < 0.05). RESULTS: After multivariate analysis, extra-alveolar time longer than 1 h was significantly associated with external root resorption. No significant association was observed between IL4 gene polymorphisms and root resorption. CONCLUSION: No association between root resorption and IL4 gene polymorphisms was observed. An extra-alveolar time of more than 1 h was associated with a susceptibility for external root resorption. Replanting the tooth in its socket immediately is the most important factor to maintain a healthy root surface.

The effect of potassium diclofenac and dexamethasone on MMP-1 gene transcript levels during experimental tooth movement in rats.

OBJECTIVES: The aim of this study was to analyze MMP-1 transcript levels in periodontal tissues of rats that underwent orthodontic treatment using potassium diclofenac and dexamethasone at different stages of tooth movement. SETTING AND SAMPLE POPULATION: The sample comprised of ninety male Wistar rats. MATERIAL AND METHODS: A closed nickel-titanium coil spring was used to apply a force of 50 cN to move the maxillary right first molars mesially. One group received daily doses of 0.9% saline solution, the second group received daily doses of 5 mg/kg potassium diclofenac, and the third group received daily doses of 0.5 mg/kg dexamethasone. Tooth movement was observed on days 0, 1, 3, 7, and 14. MMP-1 transcript levels were evaluated by real-time polymerase chain reaction and the results were compared between groups by three-way ANOVA, with a significance level of 0.05. RESULTS: Transcript levels increased in groups that received the coil spring treatment on all days of the experiment. MMP-1 expression was found to be decreased in groups treated with potassium diclofenac and dexamethasone compared to that in the control group, on days 1, 3, 5, and 7. CONCLUSIONS: The application of orthodontic forces significantly increased MMP-1 transcript levels. The use of anti-inflammatory drugs may have an inhibitory effect on MMP-1 expression.

Complete physical mapping of IL6 reveals a new marker associated with chronic periodontitis.

BACKGROUND AND OBJECTIVE: Interleukin-6 (IL-6) is a powerful stimulator of osteoclast differentiation and bone resorption. Production of IL-6 is modulated by polymorphisms, and higher levels of this cytokine are found locally in patients with chronic periodontitis. In this study we performed a modern approach - Complete physical mapping of the IL6 gene - to identify the polymorphisms associated with chronic periodontitis in a southern Brazilian population sample. MATERIAL AND METHODS: One-hundred and nine individuals of both genders (mean age: 41.5 ± 8.5 years) were divided into a study group (56 participants with periodontitis) and a control group (53 individuals without periodontitis). After collection and purification of DNA, nine tag single nucleotide polymorphisms (SNPs; rs1524107, rs2069835, rs2069837, rs2069838, rs2069840, rs2069842, rs2069843, rs2069845 and rs2069849) covering the entire gene were selected according to the information available on the International HapMap Project website and evaluated using real-time PCR. RESULTS: Differences in the distribution of the following parameters were statistically significant between study and control groups: number of teeth (p = 0.030); probing depth (p < 0.001); clinical attachment level (p < 0.001); gingival index (p < 0.001); plaque index (p = 0.003); calculus index (p < 0.001); and dental mobility (p < 0.001). It was found that marker rs2069837 (located in intron 2 of IL6) under G dominant was associated with protection against chronic periodontitis in a Brazilian population in the presence of clinical variables, such as visible plaque, dentist visit frequency and dental floss use, and was suggested for the first time as a marker of susceptibility to chronic periodontitis. CONCLUSION: Complete physical mapping of IL6 (using tag SNPs) was carried out for the first time, unveiling allele G of polymorphism rs2069837 (located in the second intron of IL6) as a suggestive marker of protection against chronic periodontitis in a Brazilian population.

Outcome of orthodontic mini-implant loss in relation to interleukin 6 polymorphisms.

Mini-implants (MIs) are used increasingly for orthodontic anchorage and their success may require some osseointegration, which is affected by the underlying host immune-inflammatory response. Interleukin 6 (IL-6) is a cytokine expressed during the host response after a trauma or infection. The aim of this study was to investigate the association of clinical characteristics and IL6 tag single nucleotide polymorphisms (which capture the information of the whole gene in terms of genetic variability) with the loss of MIs for orthodontic anchorage. A total of 487 patients were treated with orthodontic MIs between 2004 and 2010. After the application of inclusion and exclusion criteria, the sample comprised 104 patients with one or more MIs that had been in function for at least 6 months with no loss, and 31 patients who had lost one or more MIs. Allele A of rs2069843 and allele T of rs2069849 were suggestively associated with the loss of MIs for orthodontic anchorage and were in complete linkage disequilibrium, which means that one of them is sufficient to capture the same information. The location of installation (mandible) and the number of MIs installed per patient were also associated with the loss of MIs.

Fine-mapping of 5q12.1-13.3 unveils new genetic contributors to caries.

Caries is a multifactorial disease and little is still known about the host genetic factors influencing susceptibility. Our previous genome-wide linkage scan has identified the interval 5q12.1-5q13.3 as linked to low caries susceptibility in Filipino families. Here we fine-mapped this region in order to identify genetic contributors to caries susceptibility. Four hundred and seventy-seven subjects from 72 pedigrees with similar cultural and behavioral habits and limited access to dental care living in the Philippines were studied. DMFT scores and genotype data of 75 single-nucleotide polymorphisms were evaluated in the Filipino families with the Family-Based Association Test. For replication purposes, a total 1,467 independent subjects from five different populations were analyzed in a case-control format. In the Filipino cohort, statistically significant and borderline associations were found between low caries experience and four genes spanning 13 million base pairs (PART1, ZSWIM6, CCNB1, and BTF3). We were able to replicate these results in some of the populations studied. We detected PART1 and BTF3 expression in whole saliva, and the expression of BTF3 was associated with caries experience. Our results suggest BTF3 may have a functional role in protecting against caries.

Influence of MMP-8 promoter polymorphism in early osseointegrated implant failure.

OBJECTIVE: Dental implants consist in the treatment of choice to replace tooth loss. The knowledge that implant loss tends to cluster in subsets of individuals may indicate that host immuneinflammatory response is influenced by genetic factors. In fact, genetic polymorphisms influence the osseointegration process. The objective of this study was investigate the possible relationship between C-799T polymorphism in matrix metalloproteinase 8 (MMP-8) gene and early implant failure in nonsmoker patients. METHODS AND MATERIALS: Subjects were divided into two groups: control group (100 patients with one or more healthy implants) and test group (80 patients that had suffered one or more early implant failures). Genomic DNA from oral mucosa was amplified by PCR and analyzed by restriction endonucleases. The significance of the differences in observed frequencies of polymorphisms was assessed by Chi-square. RESULTS: Statistical analysis shows that in the MMP-8 gene, the T allele in 76.25% in the test group and the T/T genotype, 63.75% in the same group, may predispose to early loss of implants osseointegrated. CONCLUSION: These results suggest that polymorphism in the promoter region of MMP-8 gene is associated with early implant failure. This polymorphism can be a genetic marker to risk of implant loss. CLINICAL RELEVANCE: The determination of this genetic pattern in osseointegration would enable the identification of individuals at higher risk to loss implant. Thus, genetic markers will be identified, contributing to an appropriate preoperative selection and preparation of strategies for prevention and therapy individualized to modulate the genetic markers and increase the success rate of treatments.

A major gene effect controls resistance to caries.

Despite recent advances revealing genetic factors influencing caries susceptibility, questions regarding the model of inheritance involved are yet to be addressed. We conducted a Complex Segregation Analysis on decayed teeth in a sample of homogenous, isolated families recruited from the Brazilian Amazon. A dominant, major gene effect controlling resistance to phenotype was detected. The frequency of the resistance allele "A" was 0.63; mean numbers of decayed teeth were 1.53 and 9.53 for genotypes AA/AB and BB, respectively. These results represent a step toward a description of the exact nature of the genetic risk factors controlling human susceptibility to caries.

Screening of reducing agents for anaerobic growth of Candida albicans SC5314.

This study aimed to evaluate the influence of different redox potentials (Eh) on cell growth, whole-cell protein profile and cell surface hydrophobicity (CSH) of Candida albicans SC5314. The yeast was grown in YNB broth enriched with reducing (158mM sodium sulfite, 4mM sodium sulfite, 2.5mM sodium metabisulfite, 1.3mM 2-mercaptoethanol, 5.5mM thioglycolic acid, and 3.2mM l-cysteine hydrochloride) and oxidizing agents (15mM ammonium persulfate and 80mM potassium ferricyanide) and incubated in normoxic and anoxic atmospheres at 37°C, for 48h. Pre- and post-incubation Eh values were determined and cytoplasm proteins were extracted. Proteins were parted by SDS-PAGE and their profiles were compared. 3.2mM l-cysteine and 1.3mM 2-mercaptoethanol promoted and maintained negative Eh values during incubation. No differences were detected among SDS-PAGE profiles. CSH differences only were observed with 4mM sodium sulfite and 3.2mM l-cysteine. Results showed that 3.2mM l-cysteine is a reducing agent that allows maintenance of negative Eh in both anoxic and normoxic conditions and it seems not to interfere in the global expression of plasmatic proteins.

A critical review: an overview of genetic influence on dental caries.

Dental decay is a complex, chronic disease and one of the most common illnesses in dentistry today. Several dental decay risk factors have been identified during the last years; however, these variables alone may not entirely explain the disease development. Genetic research applied to dental decay began in the 1930s with experimental reports in animals and human observational research. Only recently, have some studies begun to search for genetic polymorphisms in humans and apply linkage analysis. However, due to the complex characteristics of the disease, the strong influence from several biological and environmental factors, and the small number of genetic studies related to dental caries, the genetic basis still requires further study. Therefore, the aim of this review is to provide a brief description of the current methodology for genetic analysis of complex traits, followed by a comprehensive evaluation of the literature related to genetic susceptibility/resistance to dental decay and a discussion of different aspects of the applied methodology. Advances towards the elucidation of the dental decay genetic basis may contribute to the understanding of the disease etiopathogenesis and to the identification of high risk groups, thus providing potential targets for effective screening, prevention and treatment.

Tumor necrosis factor-alpha -308G/A single nucleotide polymorphism and red-complex periodontopathogens are independently associated with increased levels of tumor necrosis factor-alpha in diseased periodontal tissues.

BACKGROUND AND OBJECTIVE: Inflammatory cytokines such as tumor necrosis factor-alpha are involved in the pathogenesis of periodontal diseases. A high between-subject variation in the level of tumor necrosis factor-alpha mRNA has been verified, which may be a result of genetic polymorphisms and/or the presence of periodontopathogens such as Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola (called the red complex) and Aggregatibacter actinomycetemcomitans. In this study, we investigated the effect of the tumor necrosis factor-alpha (TNFA) -308G/A gene polymorphism and of periodontopathogens on the tumor necrosis factor-alpha levels in the periodontal tissues of nonsmoking patients with chronic periodontitis (n = 127) and in control subjects (n = 177). MATERIAL AND METHODS: The TNFA -308G/A single nucleotide polymorphism was investigated using polymerase chain reaction-restriction fragment length polymorphism analysis, whereas the tumor necrosis factor-alpha levels and the periodontopathogen load were determined using real-time polymerase chain reaction. RESULTS: No statistically significant differences were found in the frequency of the TNFA -308 single nucleotide polymorphism in control and chronic periodontitis groups, in spite of the higher frequency of the A allele in the chronic periodontitis group. The concomitant analyses of genotypes and periodontopathogens demonstrated that TNFA -308 GA/AA genotypes and the red-complex periodontopathogens were independently associated with increased levels of tumor necrosis factor-alpha in periodontal tissues, and no additive effect was seen when both factors were present. P. gingivalis, T. forsythia and T. denticola counts were positively correlated with the level of tumor necrosis factor-alpha. TNFA -308 genotypes were not associated with the periodontopathogen detection odds or with the bacterial load. CONCLUSION: Our results demonstrate that the TNFA -308 A allele and red-complex periodontopathogens are independently associated with increased levels of tumor necrosis factor-alpha in diseased tissues of nonsmoking chronic periodontitis patients and consequently are potentially involved in determining the disease outcome.

Analysis of the association of polymorphism in the osteoprotegerin gene with susceptibility to chronic kidney disease and periodontitis.

BACKGROUND AND OBJECTIVE: Chronic kidney disease (CKD) is a complex disorder, which results in several complications involving disturbance of mineral metabolism. Periodontal disease is an infectious disease that appears to be an important cause of systemic inflammation in CKD patients. Periodontal disease is characterized by clinical attachment loss (CAL) caused by alveolar bone resorption around teeth, which may lead to tooth loss. Osteoprotegerin (OPG) is a key regulator of osteoclastogenesis. Polymorphisms are the main source of genetic variation, and single nucleotide polymorphisms (SNPs) have been reported as major modulators of disease susceptibility. The aim of this study was to investigate the association of a polymorphism located at position -223 in the untranslated region of the OPG gene, previously known as -950, with susceptibility to CKD and periodontal disease. MATERIAL AND METHODS: A sample of 224 subjects without and with CKD (in hemodialysis) was divided into groups with and without periodontal disease. The OPG polymorphism was analyzed by polymerase chain reaction and restriction fragment length polymorphism. RESULTS: No association was found between the studied OPG polymorphism and susceptibility to CKD or periodontal disease. CONCLUSION: It was concluded that polymorphism OPG-223 (C/T) was not associated with CKD and periodontal disease in a Brazilian population. Studies on other polymorphisms in this and other genes of the host response could help to clarify the involvement of bone metabolism mediators in the susceptibility to CKD and periodontal disease.

Analysis of the MMP-9 (C-1562 T) and TIMP-2 (G-418C) gene promoter polymorphisms in patients with chronic periodontitis.

BACKGROUND: Matrix metalloproteinases (MMP)-9 is an important member of the matrix metalloproteinase family. A functional polymorphism has been described in the promoter region of the human MMP-9 gene. A C-to-T base exchange at -1562 creates two different alleles, and the C/T and T/T genotypes promote high activity of the MMP-9 gene promoter, increasing the risk for inflammatory diseases. The metalloproteinase-2 tissue inhibitor (TIMP-2) regulates the activity of MMPs in the extracellular matrix, and a polymorphism at the -418 position of the TIMP-2 gene promoter has been found in a Sp-1 binding site. In this study we have investigated the association between the above-mentioned polymorphisms and chronic periodontitis severity. METHODS: Genomic DNA from oral mucosa of 100 subjects was amplified by polymerase chain reaction and analysed by restriction endonuclease digestion. The significance of the differences in observed frequencies of polymorphisms in moderate and severe disease and healthy groups was assessed by chi(2) test (p<0.05). RESULTS: No association was observed between the polymorphism in the promoter region of MMP-9 (p=0.6693) and chronic periodontitis. The analysis of TIMP-2 showed that the G/G genotype was found at a frequency of 99%. CONCLUSION: The results show that the polymorphism in the promoter region of MMP-9 gene is not associated with chronic periodontitis. The high frequency of GG genotype in the TIMP-2 gene promoter in the population studied did not allow any conclusion regarding its effect on chronic periodontitis.

Inhibition of human pulpal gelatinases (MMP-2 and MMP-9) by zinc oxide cements.

The interaction between metal ions and the oral environment is a major subject matter in dental research. Matrix metalloproteinases (MMPs) have been implicated in several pathological and physiological processes such as, periodontal tissue destruction, root caries, dentin calcification and pulpal inflammation. The aim of this work was to test the effect of zinc released from zinc oxide-eugenol (ZOE) cements, on the activity of the major pulpal gelatinolytic MMPs. Pulpal explants were cultured overnight in Dulbecco's Modified Eagle Medium and the activity of secreted enzymes was analysed by gelatin zymography in buffer conditioned with diverse ZOE cements. Phenanthroline, a zinc chelator, was used to revert the inhibition of MMPs caused by zinc. The major gelatinolytic proteinases present in the conditioned media were characterized as MMP-2 and MMP-9 by immunoprecipitation. All ZOE cements inhibited MMPs activity, whereas phenanthroline could partially revert the inhibition caused by plain ZOE and Intermediate Restorative Material (IRM).

Analysis of the TGF-beta1 promoter polymorphism (C-509T) in patients with chronic periodontitis.

BACKGROUND: A polymorphism in the promoter region of the transforming growth factor beta-1 (TGF-beta1) gene was described at position -509. This polymorphism represents a C-to-T base exchange, which creates a YY1 consensus sequence in an area involved with down transcription regulation. This polymorphism has been associated with risk for asthma and allergies. In this study we investigated the association between this polymorphism and chronic periodontitis severity. METHODS: Genomic DNA from oral mucosa of 87 Caucasian subjects was amplified by PCR, and digested with Eco81I restriction endonuclease. The alleles were separated by polyacrylamide gel electrophoresis. The differences in genotype distribution from those expected by Hardy-Weinberg equilibrium, and the significance of the differences in observed frequencies of the polymorphism in moderate and severe disease and healthy groups were assessed by the chi2 test. RESULTS: There was a difference in the presence of the different alleles and genotypes among the healthy, moderate and severe periodontitis groups. The allele T was seen at 57.7% in the group with severe periodontitis and 37.8% and 35.4% in the healthy group and moderate periodontitis group, respectively (p=0.0387). The genotype T/T was found at 38.5% in the group with severe periodontitis, and at a frequency of 8% in the healthy group (p=0.0258). CONCLUSION: These results demonstrate that the polymorphism at bp -509 in the TGF-beta1 promoter may have a small effect on the modulation of the inflammatory process during periodontitis.

Polymorphism at position -174 of IL-6 gene is associated with susceptibility to chronic periodontitis in a Caucasian Brazilian population.

BACKGROUND: Interleukin-6 (IL-6) is a multifunctional cytokine that mediates inflammatory tissue destruction. A G to C substitution at position -174 in the promoter of IL-6 gene reduces in vitro transcription of IL-6. This polymorphism has been associated with inflammatory diseases like chronic arthritis. OBJECTIVE: The aim of this study was to investigate the association between the IL-6-174 polymorphism and susceptibility to chronic periodontitis in Brazilians. MATERIAL AND METHODS: Eighty-four nonsmoking subjects over 25 years (mean age 42.4) were divided according to the severity level of periodontal disease: 36 healthy individuals (control group), 24 subjects with moderate and 24 with severe periodontitis. Genomic DNA was obtained from epithelial cells through a mouthwash with 3% glucose and scraping of oral mucosa. The samples were analyzed for IL-6-174 polymorphism using PCR-RFLP. The significance of the differences in the frequencies of the polymorphism in the control and groups with periodontitis was assessed by chi2 test (p<0.05). RESULTS: Differences were found between control and groups with periodontitis in the genotype (p=0.0036, OR=3.0) and in the allele (p=0.0838, OR=1.9) frequencies. CONCLUSION: We concluded that the IL-6-174 polymorphism is associated with susceptibility to chronic periodontitis in the population studied.

MMP-1 promoter polymorphism: association with chronic periodontitis severity in a Brazilian population.

BACKGROUND: A single nucleotide polymorphism was described in the promoter region of the human MMP-1 gene, and this polymorphism has been associated with risk of cancer metastasis and inflammatory diseases. In this paper, we studied the possible relationship between the MMP-1 promoter polymorphism and the severity of chronic periodontitis. METHODS: Genomic DNA from oral mucosa was amplified by PCR and analyzed by restriction endonuclease. The alleles were separated by polyacrylamide gel electrophoresis. The significance of the differences in observed frequencies of polymorphism in moderate and severe disease and healthy groups was assessed by Chi-squared test. RESULTS: In the healthy group, the 2G allele was observed with a frequency of 48.7%, while in severely diseased patients the 2G allele was seen in 69.2% (P = 0.0344). The genotype 2G/2G was found in 46.15% of the group with severe periodontitis, and 24.3% and 25.0%, respectively, of the healthy and moderate groups (P = 0.0647). CONCLUSION: These results show that a polymorphism in the promoter region of MMP-1 gene is associated with the severe chronic periodontitis phenotype in non-smokers.

Frequencies of the -330 (T --> G) IL-2 and -590 (T --> C) IL-4 gene polymorphisms in a population from south-eastern Brazil.

Polymorphisms in the promoter regions of cytokine genes may affect their transcription. A T/G substitution at position -330 of the interleukin-2 (IL-2) gene and a T/C substitution at position -590 of the interleukin-4 (IL-4) gene have been described previously. The -590 (T --> C) IL-4 gene polymorphism was associated with asthma and atopy in US and Japanese populations. Population genetics is a useful tool for determination of the biological significance of genetic polymorphisms. The aim of this study was to investigate the frequencies of polymorphisms in the promoter regions of the IL-2 and IL-4 genes in a population from south-eastern Brazil and to compare them with those published for other populations. Allele frequencies were estimated in 114 unrelated individuals from São Paulo State. These subjects had an average age of 41.2 years (+/- 12.4 years) and the ethnic composition of the sample was: 78.07% Caucasian, 11.4% Black and 10.53% Mulatto. DNA from subjects was extracted from epithelial buccal cells, and the PCR-RFLP technique was employed to investigate the -330 (T --> G) IL-2 and -590 (T --> C) IL-4 gene polymorphisms. The allele frequency of the IL-2 gene polymorphism obtained in our study was similar to that found in UK Caucasoid groups. The T allele frequency of the IL-4 gene polymorphism observed in the Caucasian Brazilian group was similar to that found in UK and Australian populations, while the frequency observed for the Black Brazilian group was similar to that found in Japanese and Kuwaiti Arab populations. The results for the -330 (T --> G) IL-2 and -590 (T --> C) IL-4 polymorphisms are consistent with the high contribution of European lineages to the population in south-eastern Brazil.

Absence of mutations in the homeodomain of the MSX1 gene in patients with hypodontia.

Hypodontia, the congenital absence of one or a few permanent teeth, is one of the most frequent alterations of the human dentition. Although hypodontia does not represent a public health problem, it may cause both speech and masticatory dysfunction and esthetic problems. A missense mutation in the homeodomain of MSX1 gene has been associated with hypodontia of second premolars and third molars in humans. However, another study excluded this gene as causative locus for hypodontia of incisors and premolars. To further investigate the role of the MSX1 gene in human hypodontia, we analyzed the homeobox region of the MSX1 gene in 20 individuals with different patterns of familial or isolated hypodontia. The direct sequencing of PCR products did not show any polymorphisms or mutations in the human MSX1 gene. Our results indicate that inactivation of MSX1 gene in humans must have a highly selective effect on dentition, and other genes must be involved in the cause of hypodontia in humans.