Mahssa HASSAN-NEJHAD, Morteza BAGHERI, Kamal KHADEM-VATANI, Mir Hossein SEYED MOHAMMAD ZAD, Isa Abdi RAD, Behzad RAHIMI, Ali ROSTAMZADEH and Amir RAHIMLOU

ABSTRACT

Background: Coronary artery disease is the leading cause of disability and mortality in Iran and worldwide. Tumor necrosis factor-alpha is a pro-inflammatory cytokine that plays a key role in inflammatory cascades and atherosclerosis. It regulates cytokine networks and adhesion molecule expression, and activates several signal transduction pathways, being also known as transducer of cardiovascular diseases, especially premature coronary artery disease.
Objective: The aim of the present study was to investigate tumor necrosis factor-alpha gene expression in Iranian Azeri Turkish patients with premature coronary artery disease (age ≤50 years).
Material and methods: Eighty four individuals (42 cases and 42 controls) were enrolled in the study. Total RNA was extracted from patients with premature coronary artery disease using RNX-Plus Solution (Cat. No.: RN7713C) and reverse transcribed into cDNA. The tumor necrosis factor-alpha mRNA expression level was evaluated using Real-Time PCR.
Results: The mean ± SE of fold in cases and controls were 1.1±1.08 and 1.6±3.4, respectively. The mean expression of tumor necrosis factor-alpha mRNA (fold) was not statistically different between the tested groups (P value 0.4).
Outcomes: Our outcome failed to find evidence for any association between tumor necrosis factor-alpha mRNA expression and premature coronary artery disease. Large scale, more detailed studies are further needed to prove our results and to propose other mechanisms in the pathophysiology of premature coronary artery disease.
Keywords: TNF-α, gene expression, premature coronary artery disease.

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Morteza BAGHERI and Isa Abdi RAD

ABSTRACT

Introduction: The aim of the present study was to determine the frequency of M694V, M680I and V726A mutations of the MEFV gene in 630 Azeri Turkish patients with family Mediterranean fever.
Material and Methods: The MEFV gene mutations were detected using allele-specific oligonucleotide polymerase chain reaction.
Outcomes: 630 cases with a mean age ± SD of 28.54±16.54 ranging from 2.5 to 76 years old including 268 (42.54%) males and 362 (57.46%) females, were tested. Nineteen patients were homozygote for one mutation (3.02%), 127 were heterozygote for one mutation (20.2%) and 18 were compound heterozygote for two mutations (2.86%). Mutation analysis confirmed that the most common mutation was M694V 109 (8.65%). V726A and M680I mutations accounted for 4.44% of the alleles; V726A 32 (2.54%) and M680I 24 (1.9%). In this study, compound heterozygote for M694V and V726A, M694V and M680I, and V726A and M680I mutations were found in 1.43%, 0.79%, and 0.63% from West Azerbaijan province in exon 10. Mutation was found in 164 (26.03%) of cases regarding analysis of the three most common MEFV mutations, but in 466 (73.97%) of cases, no mutation was detected. Among our samples, the frequencies of mutant genotypes were 15 (2.38%), 1 (0.15%), 3 (0.47%), 9 (1.42%), 4 (0.63%) and 5 (0.79%), regarding M694V/M694V, M680I/M680I, V726A/V726A, M694V/ V726A, M680I/ V726A and M680I/M694V, respectively. In our samples, 79 (12.53%), 26 (4.12%), and 22 (3.49%) cases had M694V/normal, V726A/normal, and M680I/normal genotypes regarding M694V, V726A, and M680I mutations, respectively.
Conclusions: The M694V mutation is the most common risk factor for family Mediterranean fever in our group.
Keywords: MEFV, FMF, M694V, M680I, V726A

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Morteza BAGHERI, Isa Abdi RAD, Nima Hosseini JAZANI, Rasoul ZARRIN and Ahad GHAZAVI

ABSTRACT

Introduction: This study was carried out to determine the frequency of the VNTR-polymorphisms at the PAH gene in the Iranian Azeri Turkish patients with phenylketonuria (PKU) and normal controls.

Material and methods: The VNTR-polymorphisms were determined by PCR in 43 PKU patients as well as 43 controls.

Outcomes: The frequencies of VNTR-alleles were 13(15.1%), 3(3.49%), 64(74.4%), 5(5.81%), and 1(1.16%) in the patients and 43(50%), 0(0%), 42(48.8%), 0(0%), and 1(1.16%) in the controls regarding 3, 7, 8, 9, and 11 repeat copies, respectively. The VNTR alleles with 12 and 13 repeats were not found in our samples. The frequencies of VNTR-genotypes were 25(58.1%), 1(2.33%), 1(2.33%), 10(23.3%), 2(4.65%), 2(4.65%), 1(2.33%), 1(2.33%), and 0(0%) in the patients and 13(30.2%), 13(30.2%), 0(0%), 16(37.2%), 0(0%), 0(0%), 0(0%), 0(0%) and 1(2.33%) in the controls regarding VNTR8/VNTR8, VNTR3/VNTR3, VNTR3/VNTR9, VNTR8/VNTR3, VNTR8/VNTR9, VNTR7/VNTR9, VNTR7/VNTR8, VNTR8/VNTR11, and VNTR3/VNTR11 genotypes, respectively. The comparisons of VNTRpolymorphisms imply that there are statistically significant differences between the patients and controls regarding VNTR3, VNTR8, and VNTR9 alleles as well as VNTR8/VNTR8 and VNTR3/VNTR3 genotypes (all P-Value <0.05). The frequency of “risk-associated genotype of VNTR8/VNTR8” was significantly higher in the cases. 

Conclusions: It is concluded that this position is heterozygous and there were statistically significant differences between patients and controls concerning the VNTR8/VNTR8 genotype. We found higher frequencies of disease-associated genotype in our samples than controls. This report is the first in its own type in the west Azerbaijani population. Further studies require assessing how this genotype predicts adverse outcomes in tested population.

Keywords: VNTR, polymorphism, PKU

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