Alpha-globin gene mutation spectrum in patients with microcytic hypochromic anemia from Mazandaran Province, Iran.

BACKGROUND: It is estimated about 7% of the world population is carriers of hemoglobin diseases. Alpha-thalassemia is one of the most common hereditary hemoglobin disorders in the world. This study investigated alpha-globin mutations in potential carriers with hypochromic and microcytic anemia from Mazandaran, in northern Iran. METHODS: A total of 859 subjects were selected; genomic DNA was extracted and examined for the presence of mutations in the alpha-globin genes. RESULTS: Mutation analysis of alpha-globin genes revealed 27 different mutations. Seven variants were seen in 91.45% of all alpha-1 and alpha-2 mutations among patients in this study. The 3.7 kb deletion is the most frequent mutation with a frequency of 49.53%, followed by PolyA2 (15.19%), -4.2 deletion (8.76%), --MED (5.84%), IVSI-5nt deletion (5.49%), Hb constant spring (3.62%), and Cd 19 (-G; 3.04%), respectively. There are also seven new variants which were reported for the first time either in alpha-1 or alpha-2 genes, including codon 9 (C > A; α2), deletion of codon 60 (AAG deletion; α2), duplication of codon 94-100 plus 3 base pairs of intron 2 (IVSII + 3; α1), codon 99 (C > A; α2), codon 108 (A > G; α2), codon 128 (A > T; α2), and codon 129 (T > G; α2), respectively. The MLPA method also revealed three rare and novel deletions in alpha-cluster region with about 30 kilobases long. CONCLUSION: This study showed an efficient identification of α-thalassemia can be achieved using standard hematological indices in our population. The details of these variations will help local genetic services for diagnostic and prenatal diagnosis services.

Significant correlation of angiotensin converting enzyme and glycoprotein IIIa genes polymorphisms with unexplained recurrent pregnancy loss in north of Iran.

BACKGROUND: Spontaneous abortion is considered as the most complex problem during pregnancy. Thrombophilia is resumed as a cause of recurrent pregnancy loss (RPL). Glycoprotein IIIa (GPIIIa) gene is involved in thrombosis and abortion. Angiotensin converting enzyme (ACE) converts angiotensin I to angiotensin II and is involved in thrombosis. The most common polymorphism in this gene is the insertion/deletion (I/D). OBJECTIVE: In this study, we analyzed the association between ACE I/D and GPIIIa c.98C >T polymorphisms in women with unexplained RPL from the north of Iran. MATERIALS AND METHODS: Sample population consisted of 100 women with unexplained RPL and 100 controls. The ACE I/D and GPIIIa c.98C>T polymorphisms were genotyped by TETRA-ARMS PCR. The association between genotypes frequency and RPL were analyzed using χ(2) and exact fisher tests. Associated risk with double genotype combinations was also investigated by binary logistic regression. RESULTS: There was significant association between ACE DD genotype and RPL (OR=2.04; 95% CI=0.94-4.44; p=0.036). ACE D Allele was also significantly associated with the RPL (OR=1.59; 95% CI=1.05-2.41; p=0.013). No significant association was observed between GPIIIa c.98C>T polymorphism and RPL. CONCLUSION: ACE I/D polymorphism may probably be a prognostic factor in female family members of women with the history of recurrent abortion.

Allele and genotype frequencies of CYP2C9 within an Iranian population (Mazandaran).

Cytochrome P450 2C9 (CYP2C9) is a polymorphic enzyme responsible for the metabolism of different drugs, some with low therapeutic index. The frequency of functionally important mutations and alleles of the gene coding for CYP2C9 shows wide ethnic variations. The present study aimed to determine the prevalence of the most common allelic variants of the CYP2C9 enzyme and to predict the genotype frequency in the Mazandarani ethnic group among the Iranian population. Genotyping of CYP2C9 allelic variants was carried out in 103 unrelated subjects by polymerase chain reaction and restriction fragment length pattern analysis. The frequencies for CYP2C9 alleles *1, *2, and *3 were 78%, 12%, and 10%, respectively. No subjects were found carrying the CYP2C19*11 allele. The frequencies of CYP2C9 genotypes *1/*1, *1/*2, *1/*3, *2/*2, *2/*3, and *3/*3 were 61%, 19%, 16%, 1.5%, 2.5%, and 0.0%, respectively. The result of the present study showed that the two inactive alleles of CYP2C9 accounted for 22% of CYP2C9 alleles in our sample versus 1.5%-29% reported in other populations. The frequencies of the studied alleles resulted in significant differences between our sample and African and Eastern Asian populations.

Frequencies of three CYP2D6 nonfunctional alleles (CYP2D6*3, *4, and *6) within an Iranian population (Mazandaran).

Although the frequencies of CYP2D6 nonfunctional alleles have been extensively studied in most populations worldwide, limited information is available for those of the Iranian population. The present study aimed to determine the frequency of three CYP2D6 nonfunctional alleles (CYP2D6*3, *4, and *6) in the Mazandarani ethnic group among the Iranian population. A total of 100 unrelated healthy subjects living in Mazandaran, a Caspian province in the north of Iran, were selected. Lymphocytic genomic DNA was genotyped by a polymerase chain reaction amplification method for detection of three nonfunctional alleles. Finally, the obtained data were used to determine the frequencies of the three alleles, and the results were compared with published data from other populations. The frequencies for CYP2D6 alleles *3, *4, and *6 were 0.5%, 9%, and 0.5%, respectively. Homozygous or compound heterozygous genotypes that predict poor metabolizer phenotype, that is, *4/*4 or *4/*6, were not found in this study. The result of the present study showed that CYP2D6*4 is the major nonfunctional allele found in Mazandarani subjects. In addition, the three inactive alleles of CYP2D6 accounted for 10% of CYP2D6 alleles in our sample versus 0.2%-25.2% reported in other populations. The frequencies of the studied alleles resulted in significant differences between our sample and East Asians, Black-Tanzanians, Saudi Arabians, and Caucasians.

Metabolic capacity of CYP2D6 within an Iranian population (Mazandaran Province).

BACKGROUND: CYP2D6 is polymorphically expressed enzyme that show marked interindividual and interethnic variation. Phenotyping of CYP2D6 provides valuable information about real-time activity of this important drug-metabolizing enzymes through the use of specific probe drugs. The aim of this study was to identify the CYP2D6 oxidation phenotype with dextromethorphan (DEX) as a probe drug in Mazandarani ethnic group among Iranian population. METHODS: The study included 71 unrelated healthy volunteers. Dextromethorphan hydrobromide (30 mg) was given orally to healthy subjects and peripheral venous blood samples (10 ml) were taken at 3 hr post-dose. Dextromethorphan and the metabolite dextrorphan (DOR) were analyzed by the HPLC method. The log DEX/DOR metabolic ratio (MR) at 3 hr plasma sample was used as the index of CYP2D6 activity and a value of 0.3 was used as the antimode separating extensive metabolizers (EM) and poor metabolizers (PM) phenotypes. RESULTS: A 560-fold interindividual variation in dextromethorphan MRs was observed in this study. Considering the antimode 0.3 in log scale, 7.04% (5/71) volunteers were identified as PMs. Conclusion : The result showed that the frequency of CYP2D6 PM phenotypes accounted for 7.04% of subjects in our samples. Despite these findings, we propose a further study in larger samples to provide a wider image and to get more valuable information upon pharmacogenetic basis for individual therapy and personalized medicine.