Influence of cytotoxic T lymphocyte antigen-4 (CTLA-4) gene polymorphisms in periodontitis

AimPersistent host inflammatory immune response against the pathogens results in the destruction of periodontal tissues. Cytotoxic T lymphocyte antigen 4 (CTLA-4) is a particularly important molecule in down-regulating T-cell expansion and cytokine production. This study aimed to assess three functional SNPs within CTLA-4 gene, ?1722 T/C, ?318 C/T, and +49 A/G in patients with aggressive or chronic periodontitis.Materials and methodsA total of 197 patients with periodontitis (71 aggressive and 126 chronic periodontitis) and 218 healthy controls were recruited. All samples were genotyped for CTLA-4 gene polymorphisms by polymerase chain reaction-amplification refractory mutation system (PCR-ARMS).ResultsThe allelic and genotype frequencies of only +49 A/G SNP were more prominence in patients with chronic periodontitis (CP) than that controls (0.0005 and 0.001, respectively). Multivariate logistic regression analysis was demonstrated that homozygosity in +49 G/G had profoundly increased susceptibility for CP, OR = 3.7 (95% CI; 1.6–8.5, P = 0.001). In addition, comparison of CTLA-4 SNPs between patients with CP and aggressive periodontitis (AgP) revealed that heterozygosity in ?1722 T/C polymorphism of CTLA-4 gene had a significantly higher risk for CP compared with AgP with a calculated odds ratio of 2.18 (95% CI; 1.17–4.06, P = 0.01).ConclusionThese results suggest that CTLA-4 gene variants might be associated to susceptibility to specific form of periodontitis and participate in the CP development.     

E-selectin and L-selectin polymorphisms in patients with periodontitis

Background amd Objective:  Periodontitis is a multifactorial disease in which environmental and genetic determinant factors contribute to individual subject's susceptibility. A DNA polymorphism in the regulating region of adhesion molecule genes is suggested to modulate the molecule's physiological effects. The aim of this study was to investigate the genetic association between the E-selectin Ser128Arg and L-selectin Phe206Leu polymorphisms and periodontitis.
Material and Methods:  DNA was isolated from the whole blood of 88 patients with periodontitis and 139 healthy individuals. All samples were genotyped for the E-selectin Ser128Arg and L-selectin Phe206Leu polymorphisms using the polymerase chain reaction with sequence specific primers.
Results:  Our findings revealed a significant difference in the Ser128Arg polymorphism of E-selectin, but not in the L-selectin polymorphism, between periodontal patients and controls. The 128Arg allele was present more frequently in patients than in healthy individuals (31.25% vs. 12.2%, p  < 0.0001). In addition, there was an association between the presence of the 128Arg allele and periodontitis (odds ratio 2.9; 95% confidence interval: 1.75–4.4, p  < 0.0001). No significant association was found between the polymorphisms tested and the subgroups of periodontal disease (i.e. chronic periodontitis and aggressive periodontitis).
Conclusion:  The findings of this study showed that the Ser128Arg polymorphism of E-selectin might contribute to the susceptibility of Iranian individuals to periodontitis.     

Prophylactic mastectomy and genetic testing: an update

PURPOSE/OBJECTIVES: To examine and discuss the possible benefits and difficulties with recommending prophylactic mastectomy to BRCA1- and BRCA2-positive women. DATA SOURCES: Published research articles, professional review articles, textbooks. DATA SYNTHESIS: Women with BRCA1 and BRCA2 mutations face a much higher risk of developing breast cancer than the general population, with limited options available for prevention. Prophylactic mastectomy has been shown to have a survival advantage in young women who carry BRCA1 and BRCA2 mutations. Challenges exist, however, in the use of prophylactic mastectomy and genetic testing. CONCLUSIONS: Methods of preventing breast cancer in BRCA1- and BRCA2-positive women currently are limited to watch-and-wait surveillance, prophylactic mastectomy, and, perhaps, chemoprevention. Genetic testing and prophylactic mastectomy each present unique challenges while offering certain benefits as well. Recent studies have shown survival advantages to BRCA1- and BRCA2-positive women who undergo prophylactic mastectomy. IMPLICATIONS FOR NURSING PRACTICE: Nurses need to be aware of the complex issues surrounding testing for BRCA1 and BRCA2 mutations and prophylactic mastectomy to be able to provide current information to patients and assist in decision making.     

Atypical presentation of multisystem disorders in two girls with mitochondrial DNA deletions

We describe two girls with atypical presentations of multisystem disorders due to deletions in mitochondrial DNA (mtDNA). One presented with painful carpopedal spasms due to hypoparathyroidism at the age of 4 years. The disease was rapidly progressive with development of truncal and limb ataxia, spastic paraparesis, muscle weakness and wasting, pigmentary retinal degeneration and sensorineural hearing loss. She had short stature and vitiligo patches, hirsutism, anaemia, diabetes mellitus and exocrine pancreatic dysfunction. The other girl presented at the age of 6 years with polydipsia, polyuria and fatigue due to renal tubular dysfunction. The disease was insidiously progressive with poor growth and development of sensorineural hearing loss, muscle weakness and truncal and limb ataxia. Morphological, enzyme histochemical and biochemical investigations indicated mitochondrial dysfunction of skeletal muscle, liver and kidney in one patient and of skeletal muscle and liver in the other. Both patients had large proportions of mtDNA molecules with deletion in liver, kidney, skeletal muscle and blood cells.Conclusion It may be concluded that symptoms from several different organs may be the first manifestation of a mtDNA deletion disorder.     

Genetic Analysis of Patients with Two Different Types of Hyper IgM Syndrome

ABSTRACT

Background: Hyper IgM Syndrome (HIGM) is a rare primary immunodeficiency in which impairment of class switching recombination (CSR) and somatic hyper-mutation (SHM) leads to recurrent infections.

Objectives: The aim of this study is to report the clinical and genetic features of six Iranian HIGM patients.

Methods: Six patients, who suspected to have HIGM based on two clinical findings, including recurrent infections and low levels of IgG and IgA and normal or elevated levels of IgM, were entered this study to undergo genetic studies. Sanger sequencing was applied to detect pathogenic mutations in CD40L and AID genes causing two most common forms of HIGM, which known as HIGM type 1 and 2, respectively.

Results: All patients who entered the study were males from unrelated families with a median age of 3.8 years. The most frequent clinical manifestation was recurrent pneumonia. Genetic studies of the patients revealed six different mutations, including five mutations in CD40L besides one mutation in AID. Two mutations in CD40L (p.F31fsX5 and p.C84S) were novel and three mutations (p. G219R, p.D62fsX18, and p.Q186X) have been previously reported. The mutation found in AID (p.E122X) was also previously described.

Conclusion: The study results may provide valuable information for prenatal diagnosis and also for genetic counseling especially for those who have a history of primary immunodeficiency in their family.