Q192R variant in paraoxonase 1 gene confers susceptibility to leiomyoma.

OBJECTIVE: Paraoxonase 1 (PON1) plays a defensive role against oxidative stress by destroying oxidized lipids. Q192R single nucleotide polymorphism of PON1 gene alters the enzyme's activity. Several investigations reported a link between Q192R and an increased risk of developing tumors including uterine leiomyomas. We assessed the antioxidant effects of Q192R on myoma which fluctuate in frequency between populations. STUDY DESIGN: The cohort consisted of 68 unrelated uterine leiomyoma patients and 93 healthy controls that were randomly selected from women with no ultrasonographic evidence of myoma. MATERIALS AND METHODS: Genotyping was performed using tetra-primer amplification refractory mutation system-polymerase chain reaction. Chi-square test was selected to evaluate differences between the groups. RESULTS: To analyze the correlation between PON1 Q192R and leiomyoma risk, the AA genotype was given as a reference genotype then the two other genotypes were compared with the reference. A significantly (P < 0.05) increased risk of myoma was observed with both Q192R homozygote GG and heterozygote AG genotypes. The odds ratio (OR) of AG genotype was calculated 1.8 (confidence interval [CI]: 0.94-3.62). A higher OR was seen with GG genotype (OR: 2.8; 95% CI: 0.98-8.18). CONCLUSION: Oxidative stress has been suspected of having a link with tumor development, and the role of endogenous-free radical scavenger is taken into consideration. Increased protein oxidative stress status and reduced antioxidant capacity have been observed in leiomyomas patients. Our study indicates that the low-antioxidant PON1 R192 allele correlates to leiomyoma development.

The effects of amantadine on traumatic brain injury outcome: a double-blind, randomized, controlled, clinical trial.

INTRODUCTION: Amantadine, as a dopamine receptor agonist, may stimulate and help the recovery of the nervous system after traumatic brain injury (TBI). METHODS: We performed this study as a double-blind, randomized, controlled clinical trial with target population including all patients with TBI who scored nine or lower on the Glasgow Coma Scale (GCS), admitted to our hospital between January 2013 and April 2014. The protocol included administration of the drug (placebo or amantadine) for 6 weeks and patient evaluation using the GCS and FOUR score on the first, third and seventh days after the drug was started. After 6 months from starting study drug, the patients were evaluated on the Mini-Mental State Examination, Glasgow Outcome Study, Disability Rating Scale and Karnofsky Performance Scale. RESULTS: We included 40 patients in the study. The mean age of the patients was 36.77 ± 18.21. As an only important finding, the amantadine group registered an important rise between the first and the seventh day of study drug (∆GCS7-GCS1) with p-value = 0.044. CONCLUSION: Based on our findings during the first week and the 6 months (since starting drug) follow-ups, prescribing amantadine did not lead to reportable effects on the patients' level of consciousness, memory, disability, cognition, mortality and performance.

Association of SP-B gene 9306 A/G polymorphism (rs7316) and risk of RDS.

BACKGROUND: Respiratory distress syndrome (RDS) is a severe pulmonary disease predominantly affects preterm newborns. Polymorphisms of surfactant-protein genes have been mostly evaluated as the candidate contributors in genetics of RDS. However the results are divers in different studies. We aimed at investigating the association of surfactant protein B (SPB) gene 9306 A/G polymorphism (rs7316) with RDS development. METHOD: Three hundred and eighty newborns with gestational age of less than 34 weeks were included in a multicenter case-control study. Respiratory distress (RD) was scored according to Downes' scoring system. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used for genotyping. RESULT: One hundred and eighty-four neonates showed RDS and 196 did not. Gestational age (GA) was significantly lower in the RDS group compared with the controls. AA genotype and A allele were found more frequently in the RDS group than the controls (96.2% versus 63.8% and 98.1% versus 80.6%, respectively) (p =.0001). CONCLUSIONS: This is the first report of association of SFTPB rs7316 polymorphism with RDS development in Iranian newborns. The current study suggests that GA <28-weeks is the most important factor in predisposition to RDS. Genetic background in terms of SP-B gene might be involved in predisposition to RDS in premature neonates.

Association of SP-C gene codon 186 polymorphism (rs1124) and risk of RDS.

BACKGROUND: Respiratory distress syndrome (RDS) is a severe pulmonary disease that mainly affects preterm neonates. Surfactant-protein genes' polymorphisms have been mostly evaluated as the candidate contributors in genetics of RDS. However, the results are diverse in different populations. We aimed at investigating the association of rs1124 with RDS development. METHOD: Three hundred and thirty five preterm neonates were enrolled in a multicenter case-control study. Respiratory distress (RD) was scored according to Downes' scoring system. Genotyping was performed by PCR-RFLP method. RESULT: One hundred and sixty six neonates showed RDS and 169 did not. Gestational age (GA) was significantly lower in RDS group compared to the controls. In female preterm newborns, AA genotype was found more frequently in RDS group. In RDS group, AA genotype was also associated with milder RD irrespective of gender. In neonates who were born 28-34 weeks, RD appeared to be more severe in the RDS group and males. CONCLUSIONS: This is the first report of association of SFTPC rs1124 polymorphism with RDS development in Iranian newborns. The current study suggests that GA <28-weeks is the most important factor in predisposition to RDS. AA genotype is also, a predisposing factor for the development of RDS in female preterm infants.

Association of ABO and Colton Blood Group Gene Polymorphisms With Hematological Traits Variation.

Hematological parameters are appraised routinely to determine overall human health and to diagnose and monitor certain diseases. In GWASs, more than 30 loci carrying common deoxyribonucleic acid (DNA) polymorphisms have been identified related to hematological traits. In this study, we investigated the contribution of ABO rs2073823 along with AQP1 rs1049305 and rs10244884 polymorphisms in hematological traits variation in a cohort of Iranian healthy individuals.Genomic DNA was extracted from peripheral blood of 168 healthy volunteer. Genotyping was performed by ARMS-PCR or PCR-RFLP and confirmed by DNA sequencing. Complete blood analyses were conducted for the participants. Significant association was observed between AQP1 rs1049305 and the hematological traits including hemoglobin, hematocrit, and platelet count (P = 0.012, 0.008, and 0.011, respectively). The AQP1 rs10244884 status was also significantly linked to hemoglobin and hematocrit levels in the study cohort (P = 0.015 and 0.041, respectively). Furthermore, ABO rs2073823 polymorphism was identified as a hemoglobin and hematocrit levels modifier (both with P = 0.004).AQP1 and ABO variants appear to predict hemoglobin and hematocrit levels but not other erythrocyte phenotype parameters including red blood cell counts and red blood cell indices.

Somatic mutational analysis of MED12 exon 2 in uterine leiomyomas of Iranian women.

Uterine leiomyomas are steroid-hormone dependent tumors of myometrial smooth muscle cells that affect numerous women throughout the world. Based on previous studies, we evaluated the mutations of MED12 gene which encodes a co-activator protein involved in transcription regulation of the vast majority of RNA polymerase II-dependent genes. Exon 2 of MED12 gene was genotyped by PCR-sequencing method. To determine the proportion of mutation-containing transcripts, RNA was extracted from the tissue samples and the corresponding amplified cDNA was sequenced. We observed 11 mutation positive lesions, 7 of them were located in codon 44. The c.131G>A was found to be the most common somatic mutation in this study. Our investigation also demonstrated two unreported mutations , one large deletion and one insertion. cDNA analyzing revealed that the mutated transcripts were predominantly expressed in almost all changes including the new insertion mutation c.122-123ins15. Our study provides further evidence that the MED12 somatic mutations occur in a heterozygous manner and are mostly missense mutations in codon 44. The results displayed 47.8% mutation positive lesions in Iranian patients confirming the diversity between the populations.