Nitric oxide synthase-2 (CCTTT)n polymorphism is associated with local gene expression and clinical manifestations in patients with chronic rhinosinusitis

Introduction Nitric oxide (NO) is synthesized through NO synthase (NOS). The proximal NOS2 gene promoter contains the pentanucleotide CCTTT repeat polymorphism. We examined whether CCTTT repeats are associated with NOS2 expression in the sinonasal tissues and clinical manifestations in patients with chronic rhinosinusitis. Methods Mucosal specimens were obtained from the ethmoid sinus and inferior turbinate of 30 eosinophilic chronic rhinosinusitis (ECRS) and 28 non-ECRS patients. CCTTT repeats were classified into short alleles (S), with less than or equal to 14, and long alleles (L), with more than 14. The subjects were classified into the L/S + L/L and S/S groups. Results In ECRS, the NOS2 mRNA levels of the ethmoid sinus mucosa were significantly higher in the L/S + L/L group than in the S/S group (median, 1.66 and 0.77, respectively). On the ther hand, ECRS patients showed no significant difference in the NOS2 mRNA level of the inferior turbinate between the L/S + L/L group and the S/S group (median, 0.63 and 0.88, respectively). In ECRS, preoperative SNOT-22 were significantly higher in the L/S + L/L group than in the S/S group, whereas the former group showed a lower postoperative recurrence risk. Conclusion CCTTT repeat polymorphism in the NOS2 promotor gene may be a useful indicator to evaluate ECRS severity and prognosis.

The Association between a MAOB Variable Number Tandem Repeat Polymorphism and Cocaine and Opiate Addictions in Polyconsumers

Genetic analysis of the association between alcohol, cocaine, and opiate addiction and variable number tandem repeat (VNTR) polymorphisms in monoamine oxidase B (MAOB) and serotonergic 5-hydroxytryptamine (serotonin) receptor 1B and 2C (HTR1B 21 and HTR2C) pathway genes was performed in a sample of 302 polyconsumers. Our genetic association analysis revealed a significant association between a 184 base pair (bp) VNTR polymorphism in the MAOB gene and addiction to cocaine and opiates. This work highlights new genetic marker associations in cocaine and opiate polyconsumer addictions. These data help to clarify and quantify the complex role of genetics in addictive disorders, as well as their future contribution to the prevention (genetic counselling), diagnosis (genetic diagnosis of vulnerability), and treatment (pharmacogenomics) of these disorders.

The CYP19A1 (TTTA)n Repeat Polymorphism May Affect the Prostate Cancer Risk: Evidence from a Meta-Analysis

Abnormal aromatase (CYP19A1) expression may participate in prostate cancer (PCa) carcinogenesis. However, the results of studies on the CYP19A1 gene polymorphisms and PCa are conflicting. This meta-analysis aimed to systematically evaluate the associations between the CYP19A1 Arg264Cys polymorphism and the (TTTA)n repeat polymorphism and PCa. Electronic databases (PubMed, EmBase, ScienceDirect, and Cochrane Library) were comprehensively searched to identify eligible studies. The strength of the association between the Arg264Cys polymorphism and PCa was assessed by pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) in allelic, dominant, recessive, homozygous, and heterozygous genetic models. To analyze the impact of the (TTTA)n repeat polymorphism, we sequentially took the N-repeat allele (where N equals 7,8,10,11,12, and 13) as the minor allele and the sum of all the other alleles as the major allele. The ORs and 95% CIs were calculated in the allelic model; this analysis was performed individually for each repeat number. Pooled estimates of nine studies addressing the Arg264Cys polymorphism indicated that this polymorphism was not associated with PCa risk in the overall population or in the Caucasian or Asian subgroups. The 8-repeat allele in the (TTTA)n repeat polymorphism increased PCa risk in the overall population (OR = 1.34, 95% CI = 1.14–1.58, p = .001) and in the subgroup with population-based (PB) controls (OR = 1.41, 95% CI = 1.13–1.74, p = .002) as well as in the subgroup using capillary electrophoresis to identify this polymorphism (OR = 1.34, 95% CI = 1.09–1.65, p = .006).The meta-analysis indicated that the CYP19A1 (TTTA)n repeat polymorphism, but not the Arg264Cys polymorphism, may affect PCa risk.

The CYP19A1 (TTTA)n repeat polymorphism, but not Arg264Cys polymorphism, may affect the risk of prostate cancer: evidence from a meta-analysis

Background: Abnormal aromatase (CYP19A1) expression may participate in prostate cancer (PCa) carcinogenesis. However, results of studies on the CYP19A1 gene polymorphisms and PCa are conflicting.This meta-analysis aimed to systematically evaluate the association between the CYP19A1 Arg264Cys polymorphism and (TTTA)n repeat polymorphism and PCa.Methods: Electronic databases (PubMed, EmBase, ScienceDirect, and Cochrane Library) were comprehensively searched to identify eligible studies. The strength of association between the Arg264Cys polymorphism and PCa was assessed by pooled odds ratio (OR) and 95% confidence interval (95% CI) in allelic, dominant, recessive, homozygous, and heterozygous genetic models. To analyze the impact of the (TTTA)n repeat polymorphism, we took sequentially the N-repeat allele (where N equals 7,8,10,11,12, and 13) as the minor allele and the sum of all the other alleles as the major allele. The ORs and 95%CIs were calculated in the allelic model; this analysis was performed individually for each repeat number. Results: Pooled estimates of nine studies addressing the Arg264Cys polymorphism indicated that this polymorphism was not associated with PCa risk in the overall population and in the Caucasian and Asian subgroups. The 8-repeat allele in the (TTTA)n repeat polymorphism increased PCa risk in the overall population (OR=1.34, 95% CI=1.14–1.58, P=0.001) and in the subgroup with population-based (PB) controls (OR=1.41, 95% CI=1.13–1.74, P=0.002) as well as in the subgroup of studies using capillary electrophoresis to identify this polymorphism (OR=1.34, 95%CI=1.09-1.65, P=0.006). Conclusions: The meta-analysis indicated that the CYP19A1 (TTTA)n repeat polymorphism, but not Arg264Cys polymorphism may affect PCa risk.

The Interaction of Homozygote 192-bp I nsulin-like growth factor-1 ( IGF-1) Polymorphisms and C igarette Smoking to End -stage renal disease ( ESRD)

Objective: Smoking and end-stage renal disease (ESRD) are the leading public health problems in Indonesia. Smoking is a known risk factor for the development and progression of ESRD. Specific genetic polymorphisms may modify the harmful effects of cigarette smoking and may also change the inherited risk. IGF-1 CA repeat polymorphism is thought to be associated with an increased incidence of chronic kidney disease in smokers. We investigated the impact of smoking interactions with IGF-1 CA repeat polymorphism with the rate of chronic kidney disease in Yogyakarta Special Region Indonesia. (YSRI) Result: Our study found that smoking and IGF-1 genotype 192 bp are risk factors for ESRD in Indonesia. The combination of genotype 192 bp and smoking is associated with increased ESRD events. Respondents with smoking habits and 192 bp homozygous genotype are at high risk of ESRD. Smoking habit and homozygous 192 bp genotype are strongly interaction.. There was a mild interaction between respondents with smoking habits and heterozygous 192 bp and 188 bp. There was no interaction between non-smokers with heterozygous 192 bp and 188 bp of the IGF-1 gene.

The CYP19A1 (TTTA)n repeat polymorphism, but not Arg264Cys polymorphism, may affect the risk of prostate cancer: evidence from a meta-analysis

Background: Abnormal aromatase (CYP19A1) expression has been proposed to take part in the carcinogenesis of prostate cancer (PCa).However, results of studies on the CYP19A1 gene polymorphisms and PCa are conflicting.This meta-analysis aimed to systematically evaluate the association between the CYP19A1 Arg264Cys polymorphism and (TTTA)n repeat polymorphism and PCa.Methods: Electronic databases (PubMed, EmBase, ScienceDirect, and Cochrane Library) were comprehensively searched to identify eligible studies. The strength of association between the CYP19A1 Arg264Cys polymorphism and PCa was assessed by pooled odds ratio (OR) and 95% confidence interval (95% CI) in allelic, dominant, recessive, homozygous, and heterozygous genetic models. To analyze the impact of the (TTTA)n repeat polymorphism, we took sequentially the N-repeat allele (where N equals 7,8,10,11,12, and 13) as the minor allele and the sum of all the other alleles as the major allele. The ORs and 95%CIs were calculated in the allelic model; this analysis was performed individually for each repeat number.Results: Pooled estimates of nine eligible studies addressing the Arg264Cys polymorphism indicated that this polymorphism was not associated with the risk of PCa in the overall population and in the Caucasian and Asian subgroups. A meta-analysis of six studies addressing the (TTTA)n repeat polymorphism revealed that the 8-repeat allele increased PCa risk in the overall population (OR=1.34, 95% CI=1.14–1.58, P=0.001) and in the subgroup with population-based (PB) controls (OR=1.41, 95% CI=1.13–1.74, P=0.002). Conclusions: The meta-analysis indicated that the CYP19A1 (TTTA)n repeat polymorphism, but not Arg264Cys polymorphism may affect PCa risk.

Dinucleotide (AC)n Repeat Polymorphism (rs36213840) in the Promoter Region of IL18R1 Gene and Genetic Susceptibility to Severe Malaria

Background: Cytokines are key regulator s of human immune response to malaria but polymorphisms within the regulatory or coding regions of their genes may lead to differences in expression levels which may consequently influence disease susceptibility. In this study, we characterized an adeninecytosine (AC)n dinucleotide repeat polymorphism (rs36213840) at the promoter region of the Interleukin 18 Receptor 1 (IL18R1) gene and investigated its association with severe malaria. Methods: We utilised the case-control study design to enrol a total of 207 children including 87 severe malaria cases and 120 asymptomatic controls. DNA was extracted from blood spot on filter paper using QIAamp® DNA Mini Kit (Qiagen, Hilden, Germany). Genotyping for dinucleotide repeat polymorphisms was done by PCR and capillary electrophoresis of sequenced products on ABI PRISM® 3100 DNA sequencer (PE Applied Biosystems). Results: The genotype frequencies of the dinucleotide repeats differed significantly between the two groups (χ2 = 8.69, P=0.026). We found a significantly higher frequency of the 14bp (AC)7 allele in severe malaria patients than in asymptomatic controls (odds ratio 1.945, 95% CI: 1.23 – 3.09, P = 0.005) while the frequency of the 16bp (AC)8 allele was significant higher in the asymptomatic controls than in severe cases (odds ratio 0.431, 95% CI: 0.244 – 0.761, P = 0.004). Conclusion: Results of this suggest that the 14bp (AC)7 dinucleotide repeats might be a genetic risk factor for susceptibility to severe malaria while the 16bp (AC)8 dinucleotide repeats might be a protective factor against severe malaria