ABSTRACT
OBJECTIVES: The aim of this study was to evaluate a possible relationship between DRD2/ANKK1 (rs1800497) and SLC6A3/DAT1 (rs28363170) gene polymorphisms with the response to levodopa (L-DOPA)-therapy in patients with Parkinson's disease (PD). METHODS: One hundred and ninety-five patients with idiopathic PD were investigated. Patients were genotyped for rs1800497 and rs28363170 polymorphisms using PCR-RFLP. Logistic regression was performed to assess the association of polymorphisms with the occurrence of the chronic complications of L-DOPA therapy. KEY FINDINGS: Our results showed association between the occurrence of dyskinesia with an increased greater disease severity (P = 0.007), higher L-DOPA dose (P = 0.007) and use of dopamine agonist (P = 0.020). Moreover, there were significant protective effects for age (P = 0.004) and male subjects (P = 0.006). CONCLUSIONS: Clinical and demographic characteristics of Brazilian PD patients and differences in DRD2 and DAT1 genes may to determine individual variations in the therapeutic response to L-DOPA in the Brazilian PD patients.
Subject(s)
Dopamine Plasma Membrane Transport Proteins/genetics , Levodopa/pharmacology , Parkinson Disease/drug therapy , Receptors, Dopamine D2/genetics , Adult , Age Factors , Aged , Antiparkinson Agents/administration & dosage , Antiparkinson Agents/adverse effects , Antiparkinson Agents/pharmacology , Brazil , Dose-Response Relationship, Drug , Female , Genotype , Humans , Levodopa/administration & dosage , Levodopa/adverse effects , Logistic Models , Male , Middle Aged , Parkinson Disease/genetics , Parkinson Disease/physiopathology , Polymorphism, Genetic , Protein Serine-Threonine Kinases/genetics , Severity of Illness Index , Sex Factors , Treatment OutcomeABSTRACT
BACKGROUND: The Human Papillomavirus (HPV) predisposes 500 000 women to cervical cancer. Host genetic background may facilitate virus persistence in the uterine cervix. Polymorphisms in regulatory and coding regions of cytokine genes have been associated with susceptibility to some human diseases. AIM: This study aims at investigating whether TNFA -308 G/A and IL18 -137 G/C and -607 C/A polymorphisms are associated with susceptibility to HPV infection/progression to high-grade squamous intraepithelial lesion (HSIL). SUBJECTS AND METHODS: One hundred and twenty-two HPV infected and 132 HPV negative women (the latter used as healthy controls) were analysed. TNFA -308 G/A and IL18 (-137G/C and -607 C/A) polymorphisms were analysed using specific sequence polymorphism PCR (SSP-PCR). Univariate statistical analysis and a logistic regression were performed. RESULTS: The TNFA -308A allele was associated with susceptibility to HPV infection (p = 0.0008), while the IL18 -607A allele conferred protection against HPV infection (p = 0.0043). TNFA -308 G/A and IL18 (-137G/C and -607 C/A) polymorphisms were not associated with development of cervical lesions (p > 0.05). An association was also observed between smoking and susceptibility to the development of HSIL. CONCLUSION: The findings suggest an association between two TNFA SNPs and susceptibility to HPV infection in women from Northeast Brazil. The results need to be functionally validated and replicated in other populations with different ethnic backgrounds.
