Frequency Evaluation of the CYP3A4*4 Polymorphism in Iranian Healthy Volunteers.

Purpose: CYP3A4 (cytochrome P450, family 3, subfamily A, polypeptide 4) is an important enzyme in the body. The purpose of this enzyme is to oxidize small foreign organic molecules such as drugs or toxins. The different genetic variants CYP3A4 present in individuals such as CYP3A4*4. The cytochrome P450 3A subfamily have an important role in the catabolic reactions like many of peroxidative, oxadative, and reductive biotransformation reactions of common drugs such as Carbamazepine, Hydroxylations and Nevirapine. Methods: In this study, the prevalence of CYP3A4*4 in healthy subject of Iran were analyzed. Three hundred healthy unrelated subjects were chosen. After DNA extraction, genotypes were analyzed by PCR-RFL Pand PCR-sequencing. Results: No mutation was detected for CYP3A4*4 (Ile118Val) in these individuals. This study can be a background for future studies specially pharmacogenomic investigations and association studies. In addition, this data could be help clinicians optimize therapy or recognition persons who have risk of adverse drug reactions. Conclusions: Our results show that the frequencies of the CYP3A4*4 polymorphism in Iranian population were almost similar to the other populations such as Malaysian, Indian, Taiwanese, Tepehuan Amerindians and Mestizo Mexicans. CYP3A4*4 mutation causes decrease enzyme activity in vivo because the Ile118Val mutation may affect the substrate binding and cause decrease in CYP3A4 activity. Therefore, lack of the CYP3A4*4 mutation among Iranian population renders the consumption of drugs whose metabolismis done by CYP3A4, harmless.

High prevalence of AZFb microdeletion in Iranian patients with idiopathic non-obstructive azoospermia.

Background & objectives: Genetic factors contribute about 10 per cent of male infertility. Among these, genes in azoospermia factor (AZF) region including AZFa, AZFb, AZFc and AZFd on the long arm of Y chromosome are considered most important for spermatogenesis. Deletions in these regions are thought to be involved in some cases of male infertility associated with azoospermia or oligozoospermia. We studied the incidence of AZF deletions among Iranian infertile men with idiopathic non-obstructive azoospermia. Methods: A total of 100 Iranian azoospermic infertile men were selected for the molecular study of Y chromosome microdeletions. The presence of 13 sequence tagged site (STS) markers from AZF region was investigated using multiplex polymerase chain reaction (M-PCR). One hundred fertile men were also studied as control group. Results: Twelve (12%) patients showed Y chromosome microdeletions and among these, deletion in AZFb region was the most frequent (66.67%) followed by AZFc (41.67%), AZFd (33.33%) and AZFa (8.33%), respectively. Interpretation & conclusions: Because of relatively high incidence of Y chromosome microdeletions among Iranian azoospermic patients, molecular screening may be advised to infertile men before using assisted reproductive treatments.

Mutations in corneal carbohydrate sulfotransferase 6 gene [CHST6] in Iranian macular corneal dystrophy [MCD] patients: a report of 7 patients from Iran

Macular Cornea! Dystrophy [MCD] is a rare autosomal recessive disorder affecting the stroma of cornea. Most cases of MCD are caused by mutations in CHST6 gene. The aim of this study was to determine mutations in the carbohydrate sulfotransferase 6 gene [CHST6] through genetic analysis of 7 Iranian patients with MCD. We screened the CHST6 gene to determine the range of pathogenic mutations. Genomic DMA was extracted from peripheral blood leukocytes. The coding regions of the CHST6 gene were amplified using three pairs of primers, and directly sequenced in the final step. Four mutations were found to affect the translated protein and each of them corresponded to a particular disease haplotype that has been previously reported

Molecular genetics of fetal organogenesis in the Quran: Tracking a modern concept in an original religious text

Over the recent decades, science especially in the fields of medicine and molecular genetics has been developed with incredible extension and provide us the huge bulk of new concepts in biological phenomena and all these findings result in discovering the mysteries of life more deeply. A distinct and valuable aspect of these investigations would be tracking of these newly discovered themes in original religious records. The Qur'an as an original religious text had pointed so many times to the creation of human beings and its complex process by specification. These considerations and discussions have many things in common with newly found scientific facts. This paper is a brief study between these two apparently different discussions which shows the high similarities between the facts about organogenesis stages in scientific texts with its counterpart descriptions in the Quran

Investigation on mtDNA deletions and twinkle gene mutation (G1423C) in Iranian patients with chronic progressive external opthalmoplagia.

BACKGROUND: Chronic progressive external ophthalmoplagia (CPEO) is a phenotypic mitochondrial disorder that affects external ocular and skeletal muscles and is associated with a single or multiple mitochondrial DNA (mtDNA) deletions and also nuclear gene mutations. There are also some reports about the relationship between CPEO and the nuclear Twinkle gene which encodes a kind of mitochondrial protein called Twinkle. AIMS: To study the mtDNA deletions and Twinkle gene G1423C point mutation in Iranian patients with CPEO. MATERIALS AND METHODS: We collected 23 muscle samples from patients with CPEO, 9 women (mean age 34.3 years) and 14 men (36.7 years). Multiplex polymerase chain reaction (PCR) method was used to find the presence of single or multiple deletions in mtDNA. Single stranded conformational polymorphism (SSCP) and restriction fragment length polymorphism (PCR-RFLP) methods were carried out to investigate point mutation (G1423C) in the Twinkle gene in all DNA samples. RESULTS: Different sizes of mtDNA deletions were detected in 16 patients (69.6%). Each of the 5.5, 7, 7.5 and 9 kb deletions existed only in 1 patient. Common deletion (4977bp) and 8 kb deletion were detected in 5 and 3 patients respectively. Multiple deletions were also present in 4 patients. Out of 23 patients included in our study, two cases (8.7%) had Twinkle gene mutation (G1423C) and 5 patients (21.7%) did not show any deletions in mtDNA or the Twinkle gene mutation. CONCLUSION: Our study provides evidence that the investigation of mtDNA and Twinkle gene mutations in CPEO may help with early diagnosis and prevention of the disease. Patients who did not show deletions in the mtDNA or G1423C mutation in the Twinkle gene may have other mtDNA, Twinkle or nuclear gene mutations.

Molecular analysis of the (CAG)N repeat causing Huntington's disease in 34 Iranian families.

Huntington's disease (HD) is an inherited neurodegenerative disorder characterized by chorea and progressive dementia. The mutation causing the disease has been identified as an unstable expansion of a trinucleotide (CAG) n at the 5' end of the IT 15 gene on chromosome 4. We have analyzed the distribution of CAG repeats in 71 Iranian individuals (34 patients and 37 unaffected family members) belonging to 31 unrelated families thought to segregate HD. We found one expanded CAG allele in 22 individuals (65%) belonging to 21 unrelated families. In these HD patients, expanded alleles varied from 40 to 83 CAG units and normal alleles varied from 13 to 36 CAGs. A significant negative correlation between age at onset of symptoms and size of the expanded CAG allele was found (r= - 0.51; P=0. 1). In addition, we genotyped 25 unrelated control individuals (total of 50 alleles) and found normal CAG repeats varying from 10 to 34 units. In conclusion, our results showed that molecular confirmation of the clinical diagnosis in HD should be sought in all suspected patients, making it possible for adequate genetic counseling. This Study is the first report of molecular diagnosis of Huntington disease among Iranian population and ever in Middle East and with regard to high frequency of consanguinity marriage in this region.