Higher circulating levels of chemokine CCL22 in patients with breast cancer: evaluation of the influences of tumor stage and chemokine gene polymorphism.

The receptor for CCL22 is named CCR4 that preferentially is expressed on the regulatory T cells (Treg), and accordingly, CCL22 acts as a chemoattractant for the intratumoral Treg migration. The aim of this study was to evaluate the serum CCL22 levels and a single nucleotide polymorphism (SNP) in chemokine gene, [2030 G/C (rs223818)], in patients with breast cancer. Blood samples were collected from 100 women with breast cancer before receiving chemotherapy, radiotherapy, or immunotherapy and 100 age-matched healthy women as a control group. The serum CCL22 levels were measured by ELISA. The DNA extracted and the SNP rs223818 determined by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) technique. The mean serum CCL22 levels in patients with breast cancer (2398.5 ± 123 Pg/mL) was significantly higher in comparison to healthy control group (974.2 ± 39.9 Pg/mL; P < 0.001). According to the tumor stages, the mean serum levels of CCL22 were 999.8 ± 85.0 Pg/mL in stage I, 1718.8 ± 82.3 Pg/mL in stage II, 2846.8 ± 118.0 Pg/mL in stage III, and 3954.5 ± 245.2 Pg/mL in stage IV. There was significant difference between tumor stages regarding the serum CCL22 levels (P < 0.001). In patients with breast cancer, the frequencies of CC genotype (63%) and C allele (79%) at rs223818 were significantly higher as compared to healthy controls (31 and 52%, respectively; P < 0.001). In both patients and control groups, the mean serum levels of CCL22 in subjects with CC genotype or C allele at rs223818 were also significantly higher as compared to subjects with GG genotype or G allele (P < 0.001). Higher serum CCL22 levels were observed in patients with breast cancer that is increased with advanced stages. These findings represent that the CCL22 may contribute in tumor development. The CC genotype and C allele at rs223818 were more frequent in breast cancer patients. The serum CCL22 levels were affected by genetic variations at SNP rs223818. Accordingly, SNP rs223818 may play a role in the susceptibility to breast cancer.

Higher circulating levels of chemokine CCL20 in patients with multiple sclerosis: evaluation of the influences of chemokine gene polymorphism, gender, treatment and disease pattern.

Chemokines play an important role in the autoimmune diseases. The aim of this study was to investigate the levels of CCL20 and a polymorphism [-786C > T (rs6749704)] in the chemokine gene in patients with multiple sclerosis (MS). The blood samples were collected from 135 MS patients and 135 healthy subjects as a control group. The patients have relapsing-remitting (RRMS; n = 65), primary progressive (PPMS; n = 47), secondary progressive (SPMS; n = 35) or progressive relapsing (PRMS; n = 14) patterns. The serum levels of CCL20 were measured by ELISA. The DNA was analyzed for CCL20 polymorphism using PCR-RLFP. The mean serum levels of CCL20 in the MS group were significantly higher than in the healthy group (P < 0.001). In patients with a SPMS pattern, the frequency of CT genotype at rs6749704 (24.3 %) was significantly lower as compared to patients with other patterns (42.8 %; P < 0.04). No significant differences were observed between subjects with different genotypes in rs6749704 regarding the CCL20 levels. The mean serum levels of CCL20 in both newly diagnosed and previously diagnosed patients was significantly higher than in the healthy group (P < 0.05 and 0.001, respectively). The mean serum levels of CCL20 in patients with RRMS, SPMS and PPMS patterns were significantly higher than in the healthy group (P < 0.004, P < 0.04, and 0.05, respectively). The levels of CCL20 in untreated patients and in patients who received interferon-ß, methylprednisolone or the combination of interferon-ß plus methylprednisolone were higher as compared to the control group (P < 0.05, P < 0.03, P < 0.005, and P < 0.05, respectively). These results showed higher levels of CCL20 in patients that represent that the chemokine may play an important role in the pathogenesis of MS. The rs6749704 polymorphism was an associated SPMS pattern. The levels of CCL20 were not influenced by gender, disease pattern and treatment.

Interleukin-1 receptor antagonist gene polymorphism and gingivitis in children.

AIM: To investigate the role of the polymorphism of a variable numbers of tandem repeats of interleukin-1 receptor antagonist gene (IL-1RN) on gingivitis in children. MATERIALS AND METHODS: A total of 146 Caucasian subjects (98 subjects with gingivitis and 48 controls) aged 8-12 years, were enrolled. Plaque and Calculus Indices were recorded to assess the oral hygiene. Gingival and Bleeding on Probing Indices were used to identify patients with gingivitis. DNA was extracted from epithelial cells of the cheek. Normal polymerase chain reaction was used for IL-1Ra genotyping. RESULTS: A significant association was observed between IL-1Ra gene polymorphism and gingivitis in children (P = 0.008). The IL-1RN*2 allele (A2) was significantly more frequent in controls (37%vs 22% in children with gingivitis). In addition, the carriage of A2 seemed to be protective against gingivitis, and it was more frequent in controls (60%vs 40% in children with gingivitis, P = 0.008). Moreover, multiple logistic regression analysis showed that the association between IL-1Ra gene polymorphism and gingivitis in children remained significant (P = 0.014) regardless of the significant influence of plaque (P = 0.013). CONCLUSION: IL-1Ra gene polymorphisms could have an active role in the pathogenesis of gingivitis in Caucasian children and IL-1RN*2 allele could be a protective marker against gingivitis.

Polymorphisms in the IL-10 and IL-12 gene cluster and risk of developing recurrent aphthous stomatitis.

BACKGROUND: Recurrent aphthous stomatitis (RAS) is a common, painful, ulcerative condition of the mouth. Although there is no clear genetic mode of inheritance, there is evidence that inheritance of specific gene polymorphisms may predispose individuals to RAS. AlsoTh1 cell mediated immune responses under the control of IL-10/IL-12 are thought to play an important role in its pathogenesis. OBJECTIVE: The objective of this study was to investigate the possibility that susceptibility to RAS is associated with the inheritance of specific gene polymorphisms for the T cell regulatory cytokines interleukin-10 (IL-10) and interleukin-12 (IL-12). PATIENTS AND METHODS: One hundred RAS patients and 91 ethnically matched controls were genotyped for the IL-10-592, and -1082 polymorphisms, and the IL-12 1188 polymorphism. Chi-square analysis was used to compare the allele frequencies and genotypes of cases and controls. RESULTS: No significant association was identified between inheritance of specific alleles or genotypes of the IL-10-592 and -1082 polymorphisms or IL-12 1188 polymorphism and susceptibility to RAS. CONCLUSIONS: We were unable to demonstrate an association between the inheritance of specific IL-10 or IL-12 gene polymorphisms and RAS susceptibility.

Recurrent aphthous stomatitis and gene polymorphisms for the inflammatory markers TNF-alpha, TNF-beta and the vitamin D receptor: no association detected.

OBJECTIVE: To investigate the possibility that minor recurrent aphthous stomatitis (MiRAS) is associated with the inheritance of specific gene polymorphisms for markers associated with macrophage driven inflammation, i.e. tumor necrosis factor-alpha (TNF-alpha), TNF-beta or the vitamin D receptor (VDR). SETTING: MiRAS is a common, painful, ulcerative condition of the mouth. Its etiology is unknown although mononuclear inflammatory cells are thought to play an important role. There is no clear genetic mode of inheritance, however, many patients report a positive family history and disease concordance is significantly higher in monozygotic than dizygotic twins, suggesting a polygenic mode of inheritance. METHODS: Ninety-five MiRAS patients and an ethnically matched control population were genotyped for TNFA-308, TNFB Ncol and VDR (intron 8 and exon 9) polymorphisms. Chi-square analysis was used to compare the allele frequencies and genotypes of cases and controls. RESULTS: No significant association was identified between inheritance of specific alleles or genotypes of the TNFA-308, TNFB Ncol and VDR (intron 8 and exon 9) polymorphisms and susceptibility to MiRAS. CONCLUSIONS: Inheritance of specific gene polymorphisms for TNF-alpha, TNF-beta or VDR does not appear to be a significant factor in determining susceptibility to MiRAS.

IL-1B and IL-6 gene polymorphisms encode significant risk for the development of recurrent aphthous stomatitis (RAS).

Recurrent aphthous stomatitis (RAS) is an, ulcerative condition of the mouth, with a polygenic mode of inheritance in which cytokines are thought to play an important role. Ninety-one RAS patients and 91 controls were genotyped for known IL-1A, IL-1B, IL-1RN and IL-6 gene polymorphisms. Inheritance of the G allele of the IL-1B -511 polymorphism was strongly associated with RAS (OR = 2.5, P < 0.00002), with increased numbers of G/G homozygotes (OR = 4.5, P < 0.0005). The G allele of IL-6 -174 also occurred more frequently in RAS (OR = 2.6, P < 0.0001) with greatest risk associated with G/G homozygosity (OR = 3.4, P < 0.0001). IL-1RN VNTR 1/1 homozygotes also occurred more frequently in RAS (OR = 2.0, P < 0.02). Inheritance of the G/G genotype of both IL-1B and IL-6 was a particularly strong predictor for RAS (OR = 8.5).