Is consanguineous marriage religiously encouraged? Islamic and Iranian considerations

Consanguineous marriage has had considerable attention as a causative factor in the prevalence of genetic disorders. Iran, with its majority Muslim population, has a high rate of consanguineous marriage. In Iranian tradition, first cousin marriage is an acceptable and appreciated custom. However, there seems to be no encouragement of consanguineous marriage in the Islamic context; it is merely mentioned as a traditional and common custom. This paper may help medical professionals providing premarital genetic counselling, who are regularly asked about consanguineous marriage, especially in Islamic communities. Increased public awareness via the mass media would seem to be a priority.     

C677T Methylentetrahydrofulate Reductase and Angiotensin Converting Enzyme Gene Polymorphisms in Patients with Alzheimer’s Disease in Iranian Population

In recent years numerous data suggest that vascular risk factors may be play a role in Alzheimer’s disease (AD). To determine the association of AD with methylentetrahydrofulate reductase (MTHFR) and angiotensin converting enzyme (ACE) as two main vascular risk factors, we examined MTHFR C677T and ACE insertion/deletion (I/D) gene polymorphism in 117 late-onset AD cases and 125 controls. We found no difference in ACE I/D genotype distribution between AD cases and control (P > 0.05) but there was a significant association between AD and the common MTHFR polymorphism C677T. The T allele conferred an increased risk of AD compared to carrying a C allele (P = 0.001, OR = 1.97, 95% CI: 1.3–2.09). Our result suggests a significant increase in risk of AD in cases with the MTHFR T allele, atleast in the Iranian population.     

ATM haplotypes and associated mutations in Iranian patients with ataxia–telangiectasia: recurring homozygosity without a founder haplotype

Ataxia–telangiectasia (A–T) is an autosomal recessive disorder caused by mutations in the ATM gene. The ATM gene spans more than 150 kb at chromosomal region 11q23.1 and encodes a product of 3,056 amino acids. The ATM protein is a serine/threonine protein kinase and is involved in oxidative stress, cell cycle control, and DNA repair. We analyzed the 11q22-23 haplotypes and associated mutations of 16 Iranian families. We utilized standardized short tandem repeat (STR) haplotypes to enhance mutation identification. In addition to the STR markers, single-nucleotide polymorphism haplotypes were determined, using three critical polymorphisms. The entire gene was screened sequentially by protein truncation testing, single-strand conformation polymorphism, and denaturing high-performance liquid chromatography to identify the disease-causing mutations. Of the expected 32 mutations, 25 (78%) were identified. All but two mutations led to a truncated or null form of the ATM protein (nonsense, splice site, or frameshift). Twelve mutations were identified for 15 haplotypes. Five mutations were novel. Mutations were located throughout the entire gene, with no clustering. Despite the absence of an Iranian founder mutation, three-fourths of the families were homozygous, suggesting that many undetected ATM mutations still exist in Iran. This study establishes a database for Iranian A–T families, and extends the global spectrum of ATM mutations.     

Mercury Exposure Assessment in Iranian Pregnant Women’s Hair with Respect to Diet, Amalgam Filling, and Lactation

Our aim for carrying out this study was to estimate the levels of mercury in the hair of pregnant women and its association with fish consumption and amalgam fillings. From November 2007 to January 2008, 100 hair samples were collected randomly from three groups of pregnant women: Ahvaz in the south of Iran, Noushahr in the north, and the countryside of Noushahr. Significant differences were found in these three groups of pregnant women's samples (p>0.05). The mean mercury level in women's hair was found to be 0.37 μg/g (range, 0.11-3.57 μg/g). Only in 2 % of collected hair samples did the total mercury (THg) level exceed the United States Environmental Protection Agency-recommended 1.0 μg/g. In addition, there was a positive correlation of THg content in Ahvaz group's samples with respect to fish consumption (r=0.41, p=0.02) and a negative correlation of THg content in those who consumed vegetables and fruit. The level of education also played an indicating factor in this group. Moreover, significant association was found between the residence time and Hg concentration of women's hair samples collected from Noushahr (p>0.05). Similarly, the same correlations were found between hair mercury levels and the time since the first filling, number of dental fillings, pregnancy interval, and lactating period.     

PTGS2 (COX2)??765G>C gene polymorphism and risk of sporadic colorectal cancer in Iranian population

Colorectal cancer (CRC) is one of the leading cancers worldwide. Through genome wide association studies, several single nucleotide polymorphisms scattered in the genome emerged to be influential in the development of sporadic CRC in some populations. However, replicative studies failed to prove a particular SNP-CRC association in populations and ethnic groups. Cyclooxygenase-2 (PTGS2) is a crucial enzyme involved in the metabolism of prostaglandins. The aim of this replicative study is to investigate the possible association between PTGS2?-765G>C polymorphism and sporadic CRC risk in a subset of Iranian population. A total of 110 patients with sporadic CRC, and 120 controls were genotyped for PTGS2?-765G>C polymorphism by using polymerase chain reaction-based restriction fragment length polymorphism. There were no significant differences in the genotype and allele frequencies of PTGS2?-765G>C between two groups except in irregular aspirin or non-steroidal anti-inflammatory drugs (NSAID) consumers. Frequencies of genotypes and alleles were as follows: GG?=?44.2, GC?=?48.3, CC?=?7.5%, in controls and GG?=?34.55, GC?=?60.9, CC?=?4.55% in cases. Regarding the allele frequency, the following values were found: G?=?65, C?=?35% in cases and 68.3, 31.7% in the controls, respectively. In irregular aspirin or NSAID consumers combined GC+CC genotype was found to be a risk genotype (OR?=?1.933, 95% CI: 1.067-3.501, P?=?0.036). Overall, no significant relation was found between this polymorphism and sporadic CRC in Iranians. However, in irregular aspirin or NSAID consumers the combined GC+CC genotype proved to be a risk genotype.     

Associations between C1431T and Pro12Ala variants of PPARγ gene and their haplotypes with susceptibility to metabolic syndrome in an Iranian population

Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear hormone receptor that regulates a number of genes involved in lipid and carbohydrate metabolism. The aim of this study was to investigate the association of C1431T and Pro12Ala polymorphisms of PPARγ gene and their haplotypes and diplotypes with risk of metabolic syndrome (MetS) in an Iranian population. A total of 340 unrelated Iranian subjects, including 175 MetS patients and 165 normal controls were enrolled. Each group was then divided into two subgroups according to the genotype (Pro/Pro and Pro/Ala + Ala/Ala for Pro12Ala, CC and CT + TT for C1431T). Genotypes were determined using a TaqMan method. Anthropometric indices, fasting plasma glucose and fasting lipid profile were measured by routine methods. A significant difference in the frequencies of the C1431T genotypes was observed between MetS and control subjects (P = 0.014), whereas no association was found for the Pro12Ala. The T allele carriers had a significantly increased risk of MetS compared to the CC genotype (P = 0.016) even after correction for multiple-testing and adjustment for age, sex and genotype. The T allele may therefore be considered as a risk factor for MetS (P = 0.003). Analysis of combined groups showed that X/Ala-CC and Pro/Pro-X/T diplotypes were associated with a higher body weight, waist circumference and waist to hip ratio among the individuals with MetS. Moreover the Ala-T haplotype was weakly associated with a higher level of triglyceride and lower level of HDL, suggesting the possibility of an interaction between Ala and T alleles. This study suggests that the PPARγ C1431T polymorphism is related to an increased risk of MetS in an Iranian population and interacts with the Pro12Ala polymorphism, further increasing the risk of MetS.     

A Prospective Study of Selenium Concentration and Risk of Preeclampsia in Pregnant Iranian Women: a Nested Case–Control Study

Preeclampsia remains a leading cause of maternal and perinatal mortality and morbidity worldwide; however, its specific etiology still remains obscure. Some studies implicate poor maternal selenium status predisposing the mother to preeclampsia. This study was designed to determine changes in plasma selenium levels in women having preeclampsia as compared with those with normal pregnancy. In a nested case–control study, 650 normal primigravida in their first 24–28 weeks participated in the study. After 3 months of follow-up of all subjects, blood selenium levels were measured in 38 women presenting consecutively with preeclampsia and in 38 women having a normal pregnancy by atomic absorption spectrophotometry. Birth outcomes were recorded, such as gestational age at delivery, height, weight, birth head circumflex and 1-min Apgar score. Preeclampsia affects about 5.84 % of pregnancies, and in our study, there were no significant differences in age, anthropometric indices, and family history of preeclampsia between the preeclamptic and control groups. The selenium concentrations in plasma in women with preeclampsia were significantly lower as compared with those in women with normal pregnancy (70.63?±?21.41 versus 82.03?±?15.54 μg/L, p?<?0.05). Being in the bottom tertile of selenium concentration (less than 62.2 μg/L) was associated with greater risk of preeclampsia in pregnant women. The reduced selenium in the maternal circulations observed in the preeclamptic mothers support the hypothesis that insufficient selenium concentration may be a contributing factor to the pathophysiological mechanisms associated with preeclampsia, and optimizing the dietary selenium intake through supplementation could produce demonstrable clinical benefits.     

Distribution and Environmental Suitability of the Smallscaled Rock Agama,Paralaudakia microlepis （Sauria： Agamidae） in the Iranian Plateau

Predictive potential distribution modeling is of increasing importance in modern herpetological studies and determination of environmental and conservation priorities. In this article we provided results of analysis and forecasts of the potential distribution of smallscaled rock agama Paralaudakia microlepis （Blanford, 1874） using the distribution models through Maxent （www.cs.princeton.edu/- schapire / maxent）. We made an attempt for comparison of input of bioclimatic factors and characteristics of biotope distribution for three species of genus Paralaudalda. Constructed model identified dissemination of Paralaudakia microlepis enough performance （AUC = 0.972 with dispersion 0.003）. According to the map constructed, the most suitable habitats of smallscaled rock agama Paralaudakia microlepis are located in southern and eastern Iran, the west of central Pakistan and southeastern Afghanistan.     

Evaluating Drug Resistant Mutations to HCV NS3 Protease Inhibitors in Iranian Naïve Patients

International Journal of Peptide Research and Therapeutics - Hepatitis C virus (HCV) is an important causative agent of acute and chronic hepatitis. The non-structural protein 3 (NS3) of HCV...     

‘Arab invasion’ and decline,or the import of European racial thought by Iranian nationalists

Historical research on western racial theories has grown exponentially in the past few years. A number of scholars have also investigated various cases of ethnic prejudice beyond the western pale, for instance against Koreans in Japan or Muslims in India. Yet, little attention has been given to the modalities in which European nineteenth-century racial thought was adopted in other parts of the world. This article attempts to broach a discussion on this under-analysed aspect of race studies by reviewing one case, that of Arab-hatred in modern Iran. I argue that the intense hatred of Arabs in Iranian nationalist texts derives from a racialized vision of Iranian history born in nineteenth-century European texts. Racialized historiography was selectively imported by the ideologues of Iranian nationalism as it allowed them to explain Iran's weakness in terms of a loss of racial purity.     

Lack of association between interleukin-13 gene polymorphisms (−1055 C/T and +2044 G/A) in Iranian patients with lung cancer

Lung cancer is one of the leading causes of death from cancer. Both immune cells and tumor cells play a key role in lung cancer immunity by secretion of cytokines and developing type-2 cell-mediated immune response. IL-13 is an immunoregulatory cytokine affecting tumor immunosurveillance by deviation of immune response from Th1 to Th2. In the present study we sought to determine the association of single nucleotide polymorphisms (SNPs) of IL-13 gene at positions +2044 (G/A) and −1055 (C/T) and lung cancer. One hundred forty one patients and 113 controls were recruited; control group was subdivided into smoker and nonsmoker individuals for serum detection. Genotyping was carried out by PCR-RFLP assay and IL-13 detection by ELISA method. No statistically significant difference was found in the frequency of genotypes, alleles, and haplotypes at positions +2044 (G/A) and −1055 (C/T) of IL-13 gene between lung cancer patients and controls. Serum level of IL-13 was not detectable in both groups. The results of this study reveal that although +2044 (G/A) and −1055 (C/T) SNPs in IL-13 are implicated in some pulmonary processes, they do not confer susceptibility to lung cancer in Iranian population.     

Protection by zinc against UVA— and UVB-induced cellular and genomic damage in vivo and in vitro

For many years, zinc salts have been used both topically and orally to treat minor burns and abrasions as well as to enhance wound repair in man and animals. In this study we describe the protective effects of zinc against UV-induced genotoxicity in vitro and against sunburn cell formation in mouse skin in vivo. Cultured skin cells from neonatal mice showed a dramatic increase in the number of micronuclei as a result of UVA and UVB irradiation. Inclusion of zinc at 5 μg/mL in the medium significantly reduced the frequency of micronuclei and of micronucleated cells. In hairless mice, topical application of zinc chloride for 5 consecutive days or a single application 2 h prior to UV exposure reduced the number of sunburn cells in the epidermis as did application of zinc 1 h after exposure. Application 2 h after irradiation also tended to have a protective effect, although there was a large variation between animals. It is proposed that an influx of zinc can protect epidermal cells against some of the more delayed effects of UV-induced damage.     

Zinc downregulates HIF-1α and inhibits its activity in tumor cells in vitro and in vivo

Background

Hypoxia inducible factor-1α (HIF-1α) is responsible for the majority of HIF-1-induced gene expression changes under hypoxia and for the “angiogenic switch” during tumor progression. HIF-1α is often upregulated in tumors leading to more aggressive tumor growth and chemoresistance, therefore representing an important target for antitumor intervention. We previously reported that zinc downregulated HIF-1α levels. Here, we evaluated the molecular mechanisms of zinc-induced HIF-1α downregulation and whether zinc affected HIF-1α also in vivo.

Methodology/Principal Findings

Here we report that zinc downregulated HIF-1α protein levels in human prostate cancer and glioblastoma cells under hypoxia, whether induced or constitutive. Investigations into the molecular mechanisms showed that zinc induced HIF-1α proteasomal degradation that was prevented by treatment with proteasomal inhibitor MG132. HIF-1α downregulation induced by zinc was ineffective in human RCC4 VHL-null renal carcinoma cell line; likewise, the HIF-1αP402/P564A mutant was resistant to zinc treatment. Similarly to HIF-1α, zinc downregulated also hypoxia-induced HIF-2α whereas the HIF-1β subunit remained unchanged. Zinc inhibited HIF-1α recruitment onto VEGF promoter and the zinc-induced suppression of HIF-1-dependent activation of VEGF correlated with reduction of glioblastoma and prostate cancer cell invasiveness in vitro. Finally, zinc administration downregulated HIF-1α levels in vivo, by bioluminescence imaging, and suppressed intratumoral VEGF expression.

Conclusions/Significance

These findings, by demonstrating that zinc induces HIF-1α proteasomal degradation, indicate that zinc could be useful as an inhibitor of HIF-1α in human tumors to repress important pathways involved in tumor progression, such as those induced by VEGF, MDR1, and Bcl2 target genes, and hopefully potentiate the anticancer therapies.     

Trolox and ascorbate: are they synergistic in protecting liver cells in vitro and in vivo?

From in vitro studies involving multilamellar liposomes or other artificial systems, several groups of workers have deduced that Trolox (a water-soluble analogue of vitamin E) and ascorbate are synergistic antioxidants. Here, we demonstrate that while Trolox and ascorbate individually protect cultured hepatocytes against oxyradicals generated either with xanthine oxidase plus hypoxanthine or with hydrogen peroxide, the two antioxidants do not appear to be synergistic when used in equimolar combinations. Also, in a rat model of hepatic ischemia-reperfusion, we observed that infusion of Trolox or ascorbate (7.5-10 mumol/kg body weight) into the postischemic liver reduced the reperfusion injury by 76 or 67%, respectively. However, when both compounds were used together (each at the same dose as used separately), the organ salvage amounted to only 79%. Therefore, there is no evidence of synergism between Trolox and ascorbate in our in vitro and especially in vivo systems.     

Dual localization of β-glucuronidase and acid phosphatase in lysosomes and in microsomes

Summary The dual localization of certain hydrolases in lysosomes and in endoplasmic reticulum as studied in enzyme staining reactions is now supported by cytobiochemical studies on mouse liver and kidney -glucuronidase and acid phosphatase. Use was made of the renal -glucuronidase response to endogenous androgen for both studies. Accordingly, sucrose homogenates were prepared of liver and kidney of male BALB/C mice previously injected with gonadotrophin along with control animals receiving saline instead. The homogenates were subjected to differential ultracentrifugation yielding six fractions. These were characterized as to their organelle composition by measurements of marker enzymes and by observations with the electron microscope. In all subcellular fractions, -glucuronidase was uniformly increased 5 to 8 times over the corresponding control value and, in fractions rich in lysosomes, this enzyme was easily released by alternate freezing and thawing. On the other hand, the microsomal -glucuronidase and acid phosphatase enzymes were not liberated by freezing and thawing nor were they after treatment with 0.1 % Triton X-100 and by employing other reagents and conditions which are known to release lysosomal enzymes. In contrast to microsomal acid phosphatase, microsomal -glucuronidase activity could be liberated by treatment with hyaluronidase. This soluble -glucuronidase showed the same optimum pH, Michaelis Constant and heat inactivation behavior as the lysosomal -glucuronidase prepared by freezing and thawing treatment. These observations define two populations of microsomal vesicles each identifiable by an individual membrane-associated acid hydrolase. One of these -glucuronidase, increases in specific activity in the animal on androgens and is released by hyaluronidase and the other, acid phosphatase, does not respond to androgen and is not released by hyaluronidase. There would appear to be a variety of mechanisms by which hydrolases enter into association with the membranes of the endoplasmic reticulum and from there, a variety of routes to the lysosomes. A comment is made concerning the question of acid phosphatases and -glucuronidase as enzyme markers for lysosomes in mouse kidney.Aided in part by Research Grant, P-106, of the American Cancer Society, Inc., New York, and by U.S.P.H.S. Grant CA-07538 and by a Research Career Award, CA-K6-18453 to William H. Fishman.     

Interaction between Oligomers of Stefin B and Amyloid-�� in Vitro and in Cells

To contribute to the question of the putative role of cystatins in Alzheimer disease and in neuroprotection in general, we studied the interaction between human stefin B (cystatin B) and amyloid-β-(1–40) peptide (Aβ). Using surface plasmon resonance and electrospray mass spectrometry we were able to show a direct interaction between the two proteins. As an interesting new fact, we show that stefin B binding to Aβ is oligomer specific. The dimers and tetramers of stefin B, which bind Aβ, are domain-swapped as judged from structural studies. Consistent with the binding results, the same oligomers of stefin B inhibit Aβ fibril formation. When expressed in cultured cells, stefin B co-localizes with Aβ intracellular inclusions. It also co-immunoprecipitates with the APP fragment containing the Aβ epitope. Thus, stefin B is another APP/Aβ-binding protein in vitro and likely in cells.