Polymorphic variants in genes related to stress coping are associated with the awake bruxism.

BACKGROUND: Chronic stress is one of the leading predisposing factors in bruxism aetiology, but the influence of genetic factors is also suggested. We aimed to study whether sequence variants in genes involved in stress regulation pathways: NTRK2 and BDNF, may be associated with awake bruxism susceptibility, clinical presentation, and patients' perceived stress level. METHODS: The study group included 104 patients with probable awake bruxism and 191 population controls. Patients underwent dental examination concerning the symptoms of bruxism and psychological testing. Genotyping was performed using HRMA and sequencing. Statistical analyses were conducted, and P values below 0.05 were considered statistically significant. RESULTS: We observed a positive correlation of measured stress level and pathological teeth attrition in the anterior segment (r = 0.45, P < 0.001), enamel attritions (r = 0.44, P < 0.001), tongue impressions (r = 0.50, P < 0.001) and posterior teeth attrition (r = 0.27, P = 0.005). Moreover, the c.196A variant (p.66Met) of the BDNF gene and c.1397-31392G allele of the NTRK2 gene were present with elevated frequency, comparing to controls. CONCLUSIONS: This study hence the thesis that perceived stress level is a substantial contributing factor to awake bruxism occurrence and its clinical manifestations. Moreover, sequence variants in genes related to stress coping may be correlated with awake bruxism's susceptibility via elevated perceived stress level.

Modifying impact of RET gene haplotypes on medullary thyroid carcinoma clinical course.

The clinical course of medullary thyroid carcinoma (MTC) associated with the MEN2A syndrome as well as of sporadic MTC shows considerable heterogeneity. The disease picture varies not only between the same RET proto-oncogene mutation carriers but also among sporadic MTC patients with no RET germinal mutations, which suggests the involvement of additional modulators of the disease. However, genetic factors responsible for this heterogeneity of the MTC clinical course still remain unknown. The aim of this study was to determine if polymorphic variants or specific haplotypes of the RET gene may modify the MTC clinical course. We genotyped the following loci: c.73+9277T>C, c.135G>A, c.1296A>G, c.2071G>A, c.2307T>C, c.2508C>T and c.2712C>G in 142 MTC patients and controls. We demonstrated considerable differences in the genotypes distribution within c.73+9277T>C, c.135G>A and c.2307T>C loci Our results show that the c.73+9277T variant associated with a decreased activity of the MCS+9.7 RET enhancer is rare in hereditary MTC patients with primary hyperparathyroidism, and thus, may influence the MTC clinical picture. The decreased activity of the RET promoter enhancer reduces RET expression level and may counterbalance the activating mutation in this gene. Frequent co-occurrence of the c.73+9277T allele with p.E768D, p.Y791F, p.V804M or p.R844Q RET mutations may be associated with their attenuation and milder clinical picture of the disease. Haplotypes analysis showed that C-G-A-G-T-(C)-C (c.73+9277T>C - c.135G>A - c.1296A>G - c.2071G>A - c.2307T>G - (c.2508C>T) - c.2712C>G) alleles combination predisposes to pheochromocytomas and primary hyperparathyroidism. We consider that RET haplotypes defining may become an auxiliary diagnostic tool in MTC patients.

The c.470 T > C CHEK2 missense variant increases the risk of differentiated thyroid carcinoma in the Great Poland population.

BACKGROUND: Differentiated thyroid carcinoma (DTC) originates from thyroid follicular epithelial cells and belongs to a group of slowly progressing tumors with a relatively good prognosis. However, recurrences and metastases are a serious problem in advanced stages. Furthermore, progression from a well differentiated thyroid carcinoma to an aggressive anaplastic one is possible. The majority of differentiated thyroid carcinomas are sporadic but a few alleles increasing the cancer risk are known. One of them is the c.470 T > C (p.I157T, rs17879961) missense substitution in the CHEK2 gene. AIM OF THE STUDY: The aim of this study was to investigate whether this specific CHEK2 alteration, c.470 T > C, predisposes the Great Poland (Wielkopolska) population to thyroid cancer. METHODS: 602 differentiated thyroid carcinoma patients and 829 controls randomly selected from population were genotyped for the presence of the c.470C allele using pyrosequencing. Hardy-Weinberg Equilibrium (HWE) was tested for both groups by chi-square distribution and Fisher's exact test. The odds ratios (ORs), 95% confidence intervals (CIs), and p-values were calculated using the R software. RESULTS: The results of genotyping showed the presence of the c.470C allele in 51 patients with a frequency of 4.49%, while in a controls in 42 patients with a frequency of 2.53%. We demonstrated that in the Great Poland population the c.470C CHEK2 variant increases the risk of developing differentiated thyroid cancer almost twice (OR = 1.81, p = 0.004). The risk of papillary thyroid carcinoma in female patients homozygous for the c.470C allele was shown to increase almost 13-fold (OR = 12.81, p = 0.019). CONCLUSIONS: Identification of c.470C CHEK2 gene variant ought to be taken into account by healthcare policymakers. Future well-designed and larger population studies are of great value in confirming these findings. Moreover, a combination of genetic factors together with environmental exposures should also be considered.

CCND1 gene polymorphic variants in patients with differentiated thyroid carcinoma.

Alterations in the CCND1 gene affect the cell cycle and are frequently observed in a variety of cancers. While the most frequent mutations that occur in thyroid tumor tissue have been characterized, the genetic factors that predispose individuals to differentiated thyroid cancer (DTC) remain to be elucidated. The present study examined whether the CCND1 c.723G>A (rs9344; p.Pro241=) and c.669C>T (rs3862792; p.Phe223=) variants have an impact on DTC susceptibility. A cohort consisting of 652 patients diagnosed with DTC were analyzed and comapred with a reference group of 799 subjects from the general population. Pyrosequencing was used as the genotyping technique. In order to determine the statistical significance of differences observed in the genotypic and allelic frequencies between the compared groups, GraphPad Prism 4 was used. At the rs9344 locus in the DTC patients, a higher frequency of allele A [P=0.032; odds ratio (OR), 1.18; 95% confidence interval (CI), 1.014-1.361] and the AA homozygous genotype (P=0.028; OR, 1.41; 95% CI, 1.059-1.989) was observed compared with the control population group. The differences were stronger for papillary carcinomas (OR 1.45; 95% CI, 1.059-1.989), but were not significant in follicular tumors. No statistically significant differences were noted in the frequency of genotypes or alleles at the rs3862792 locus in the examined groups. The present findings indicate that the c.723A variant of the CCDN1 gene may be a susceptibility low penetrance allele in the development of papillary thyroid cancer in the population studied, however it does not impact on multifocality, metastatic ability or age at diagnosis. A cumulative effect of the analyzed CCND1 gene variants was also excluded.

[Association study between exon 4 NFKBIL1 polymorphism and multiple sclerosis]. / Analiza polimorffizmu eksonu 4 NFKBIL1 w populacji chorych na stwardnienie rozsiane.

UNLABELLED: Multiple sclerosis (MS) is conceptualised as a complex autoimmune inflammatory disorder in which several environmental factors act together in a genetically susceptible individual to cause disease. Epidemiological data confirmed that genetic factors are involved in MS pathogenesis. Genes responsible for MS predisposition still await to be identified. The only consistent genetic finding, establishes so far, is the association between MS and a number of HLA haplotypes (locus 6p21.3). NFKBIL1 gene (locus 6p21.31) is one of candidate genes. One of NFKBIL1 gene coding sequence polymorphisms is a non-synonymous thymine-cytosine substitution at position 738 (exon 4) resulting in cysteine-arginine substitution at position 224 of encoded protein. THE AIM OF THE STUDY: To assess the NFKBIL 1 exon 4 contribution to MS genetic predisposition and its relationship to the clinical course of the disease. MATERIAL AND METHODS: 107 unrelated MS patients (77 female ones) attended in Department of Neurology Medical University of Poznari participated in this study. Control group included 110 healthy age and sex matched unrelated volunteers (71 female). Investigation of NFKBIL1 exon 4 polymorphism was performed with use of the single strand conformation polymorphism technique (SSCP). RESULTS: NFKBIL1 exon 4 polymorphism was observed in 10 patients and 9 control samples (9.35% and 8.18% respectively). The results remained statistically insignificant (p = 0.8136). Associations between the polymorphism and course of MS, clinical symptoms at onset, sex (p = 0.2851) and optic neuritis (ON) (p = 0.0865) were also insignificant. However, lack of statistical significance in the two latter parameters suggests insufficient size of the patients and control groups, as the absolute percentage values were remarkably different (respectively: 7.59% female vs. 14.28% male; 2.5% ON-positive vs. 13.4% ON-negative). CONCLUSIONS: The results of the present study do not provide evidence for the association between the NFKBIL1 exon 4 polymorphism and MS predisposition in the investigated Polish population. However, it may have a restricted result on MS course and a protecting effect on optic neuritis in MS patients.

[Does smoking influence the course of Crohn's disease in patients with the presence of gene NOD2/CARD15 mutation?]. / Czy palenie papierosów ma wplyw na przebieg choroby Lesniowskiego-Crohna u chorych z obecnym wariantem mutacji genu NOD2/CARD15?

Inflammatory bowel diseases can be divided into two diseases: ulcerative colitis and Crohn's disease. It is well known that there is the influence of smoking on these course of diseases and the number of flares. This influence is different in both diseases and is definitely negative among patients with Crohn's disease. The aim of the study was to establish if there is a difference of smoking influence on the course of disease depending if the patient is the carrier of NOD2/CARD15 mutation or not. 150 patients with CD was examined by careful interview about smoking habits, physically and there was molecular analyze performed of monocytes' DNA. The most often variant of NOD2/CARD15 mutation in Polish population was 802 C>T which causes the conversion of proline into serine in 268 position of protein product. The second most often observed variant was found during the analyze of exon 11 in the temperature of 20 degrees C. There was a frameshift mutation 3020insC present in 14.9% patients with CD which causes the C insertion in 3020 position of protein product. All patients with the frameshift mutation were also carriers of 802C>T mutation. The analysed features were the course of disease, the smoking habit and the difference in group of NOD2/CARD15 carries and patients without the mutation. We took into consideration the fact if the affected person was smoker, ex-smoker or non-smoker. Patients with 802C>T mutation ex-smokers and smokers were older on the onset of the disease (average: 35.8 years), whereas the non-smokers (average: 26.07 years). And what is more interesting, the non-smoking patients were statistically less frequent operated (the partial resection of terminal ileum). Only 31.82% of non-smoking patient with 802C>T mutation were operated.