CG/CA genotypes represent novel markers in the NPHS2 gene region associated with nephrotic syndrome

Nephrotic syndrome (NS) is considered as a primary disease of the kidney that represents a heterogeneous group of glomerular disorders occurring mainly in children. It is generally divided into steroid-sensitive and steroid-resistant forms, depending upon the patient’s response to steroid therapy. Among the genes involved, the NPHS2 gene has been reported as the causative gene in steroid resistant form of nephrotic syndrome. In the present study, heterozygosity rate, allelic frequency and linkage of rs2274625 and rs3829795 markers were investigated in the NPHS2 gene region. To determine the SNP alleles, tetra-primer ARMS PCR was used. After genotyping rs2274625 and rs3829795 polymorphic markers in 120 unrelated individuals and nine trios families, the data were analysed using various computer programs such as UCSC Genome Browser, dbSNP and SNPper. Based on the statistical analysis of the results, for rs2274625 marker, allele frequency for C and T alleles was 97% and 3%, respectively. For rs3829795 marker allele frequency for G and A alleles was 55% and 45%, respectively. The values of heterozygosity index for the examined markers were 5% for rs2274625 and 45/8% for rs3829795. Consequently, two informative haplotypes, CG/CA, were identified in the NPHS2 gene region through combination of these two markers. These haplotypes can serve as appropriate tools for the identification of heterozygous carriers and linkage analysis of nephrotic syndrome disease in the Iranian families with an affected child.

Clinical features and tubulin folding cofactor E gene analysis in Iranian patients with Sanjad-Sakati syndrome / Características clínicas e análise genética e de cofatores de dobramento da tubulinaem pacientes iranianos com síndrome de Sanjad-Sakati

Abstract Objective Permanent hypoparathyroidism can be presented as part of genetic disorders such as Sanjad-Sakati syndrome (also known as hypoparathyroidism—intellectual disability-dysmorphism), which is a rare autosomal recessive disorder. Our aim was to confirm the diagnosis of a group of patients with dysmorphism, poor growth, and hypoparathyroidism clinically labeled as Sanjad-Sakati syndrome and to identify for the first time the genetic variations on Iranian patients with the same ethnic origin. Methods In this study, 29 cases from 23 unrelated Arab kindreds with permanent hypoparathyroidism and dysmorphism indicating Sanjad-Sakati syndrome were enrolled for 10 years in the southwest of Iran. The mutational analysis by direct sequencing of the tubulin folding cofactor E gene was performed for the patients and their families, as well as their fetuses using genomic DNA. Results Twenty-eight out of 29 cases had parental consanguinity. Twenty-seven cases presented with hypocalcemia seizure and two were referred because of poor weight gain and were found to have asymptomatic hypocalcemia. The dysmorphic features, hypocalcemia in the setting of low to normal parathyroid hormone levels and high phosphorus led to the diagnosis of these cases. Sequencing analysis of the tubulin folding cofactor E gene revealed a homozygous 12-bp deletion (c.155-166del) for all patients. Following that, prenatal diagnosis was performed for eight families, and two fetuses with a homozygous 12-bp deletion were identified. Conclusion These results make it much easier and faster to diagnose this syndrome from other similar dysmorphisms and also help to detect carriers, as well as prenatal diagnosis of Sanjad-Sakati syndrome in high-risk families in this population.

Resumo Objetivo O hipoparatireoidismo permanente pode estar presente como parte das doenças genéticas como na síndrome de Sanjad-Sakati (também chamada de síndrome de hipoparatireoidismo, retardo e dismorfismo), que é um distúrbio autossômico recessivo raro. Nosso objetivo foi confirmar o diagnóstico de um grupo de pacientes com dismorfismo, crescimento deficiente e hipoparatireoidismo clinicamente identificado como síndrome de Sanjad-Sakati e identificar as variações genéticas, pela primeira vez, em pacientes iranianos com a mesma origem étnica. Métodos Neste estudo, foram inscritos 29 casos de 23 famílias árabes sem parentesco com hipoparatireoidismo e dismorfismo indicando síndrome de Sanjad-Sakati, durante 10 anos no sudoeste do Irã. Foi feita a análise mutacional por sequenciamento direto do gene do cofator E de dobramento da tubulina dos pacientes e de suas famílias e também de seus fetos com o DNA genômico. Resultados Apresentaram consanguinidade parental 28 dos 29 casos. Desses, 27 casos apresentaram convulsão por hipocalcemia e dois foram encaminhados devido ao baixo ganho de peso, considerando diagnóstico de hipocalcemia assintomática. As características dismórficas, hipocalcemia na configuração de níveis de hormônio da paratireoide baixos a normais e alto nível de fósforo levaram ao diagnóstico dos casos. A análise de sequenciamento do gene do cofator E de dobramento da tubulina revelou deleção homozigótica de 12 pares de base (pb) (c.155-166del) em todos os pacientes. Após isso, foi feito o diagnóstico pré-natal em oito famílias e dois fetos foram identificados com deleção homozigótica de 12 pb. Conclusão Esses resultados tornam o diagnóstico dessa síndrome muito mais fácil e rápido do que outros dismorfismos semelhantes e também ajudam a detectar portadores, bem como o diagnóstico pré-natal da síndrome de Sanjad-Sakati em famílias de alto risco nessa população.

Accuracy of Demirjian’s Method to Estimate Chronological Age in 5‒17-Year-Old Iranian Population

Introduction:To detect physiological maturity of a child, use of dental and skeletal development can be helpful. The Demirjian’s Method is one of the commonly used methods to estimate dental age. The aim of the present study was to evaluate the validity of Demirjian method in Iranian population with different races.Materials and Methods:The present cross-sectional study was performed on a randomly selected sample of panoramic radiographs of 3073 patients aged 5‒17 years. The chronological age (CA) was calculated by subtracting the date of birth from the date on which the radiographs were taken. Estimated age (EA) was performed by Demirjian method using seven left mandibular teeth. Paired t-test was used to compare differences between chronological and estimated age.Results:The mean of CA was 11.14±2.61 years whereas the mean EA was 11.35±2.62; Original Research Article therefore, EA was calculated 2.5 months more than CA. According to paired t-test the difference between CA & EA was significant (P≤ 0.001). Pearson’s correlation coefficient showed a strong linear correlation between CA and EA in total (r=0.891, P≤0.001), in girls (r=0.895, P≤ 0.001) and in boys (r=0.876, P≤ 0.001). The new regression line equation based on Iranian standards would be CA=1.08±0.89EA in total, CA=1.09±0.89EA in girls and CA=1.12+0.88EA in boys. Conclusion:Using Demirjian’sMethod overestimated dental age in the Iranian population. A new regression line equation based on Iranian standards was obtained according to the results of the present study

Association of VDR FokI and ApaI Genetic Polymorphisms with Parkinson’s Disease Risk in South Western Iranian Population.

Background: Parkinson’s disease comes second comparing to Alzheimer’s disease being responsible for nerve destructing diseases; it is a complex and multifactorial disease. Gene associated studies help to identify the genetic factors that introduce the Single Nucleotide Polymorphisms in different genes as genetic risk factors for non-Mendelian Parkinson’s disease in diverse populations. We intended to study the association of VDR (Vitamin D Receptor) gene polymorphisms with Parkinson’s disease in south western Iranian population. Results: In the present study 150 patients with Parkinson’s disease and 160 Healthy controls from an Iranian population were genotyped for two polymorphic sites. The prevalence of VDR polymorphisms in two restriction fragment length polymorphism sites including FokI and ApaI were analyzed in patients and controls. Our data demonstrated no significant association between VDR FokI polymorphism and PD, whereas the ApaI polymorphism showed a significant association with PD in Iranian patient. Also no association between the age at onset, the male-female ratio and the VDR polymorphism in the PD group was detected. Conclusions: In conclusion these results determined that VDR ApaI (TG and GG) genotype might affect development of PD in our study population. There was no association between FokI polymorphism and the risk of PD. Our results were analogous only with American/Hungarian Caucasian race.

Distribution and genotype frequency of the C1431T and pro12ala polymorphisms of the peroxisome proliferator activator receptor gamma gene in an Iranian population.

BACKGROUND: Peroxisome proliferator activator receptor gamma (PPARγ) is a nuclear transcription factor regulating multiple genes involved in cell growth, differentiation, carbohydrate and lipid metabolism and energy production. Several genetic variations in the PPARγ gene have been identified to be associated with diabetes, obesity, dyslipidemia, insulin resistance, metabolic syndrome and coronary artery disease. The present study was designed to explore the distribution of two common single nucleotide polymorphisms of the PPARγ gene (C1431T and Pro12Ala) in an Iranian population. MATERIALS AND METHODS: Genotype frequencies for these two polymorphisms were compared for 160 healthy Iranian individuals with reports from other populations. The Genotyping was performed using real‑time polymerase chain reaction. RESULTS: The genotype distribution of the C1431T PPARγ polymorphism was 0.869 for the CC genotype, 0.119 for the CT genotype and 0.013 for uncommon TT genotype. Allelic frequencies were 0.93 for C and 0.07 for T allele respectively. For the Pro12Ala polymorphism of PPARγ gene, genotypic distributions and allelic frequencies were, 0.813 for CC, 0.181 for CG and 0.06 for GG and 0.903 for C and 0.097 for G respectively. Allelic and genotypic frequencies for both polymorphisms of PPARγ gene were in Hardy‑Weinberg equilibrium. CONCLUSIONS: Iran is a country with an ethnically diverse population and a comparison of allelic and genotypic frequencies of PPARγ C1431T and Pro12Ala polymorphisms between our population and others showed significant differences.

Association between dental caries and age-specific body mass index in preschool children of an Iranian population.

Background: The aim of this study was to determine the association of dental caries and BMI-for-age in preschool children and whether BMI-for-age is similar or different between Severe Early Childhood Caries (S-ECC) and caries free children. Materials and Methods: Four hundred preschool children aged 30-70 months were entered into this study. The parameters examined in this study were weight, height, BMI-for-age and number of decayed, extracted and filled surfaces of deciduous teeth (defs). Based on dental caries, the subjects were also divided into S-ECC and caries-free groups. Then data was analyzed by t-test, one-way ANOVA, multiple regression and logistic regression tests. Results: The mean and SD of defs index was 8.37 ± 11.2. In the underweight, normal-weight, at risk of overweight and overweight groups, these values were 4.89 ± 10.8, 8.84 ± 11.8, 8.68 ± 10.6, and 10.39 ± 10.2, respectively. Multiple regression analysis revealed a statistically a significant direct association between BMI-for-age and defs index (P = 0.001) after adjusting for gender and age. The percentage of subjects who were caries free and S-ECC was 44.8% and 51.2%, respectively. Logistic regression analysis showed that there was statistically a significant inverse association between BMI-for-age scores and the frequency of caries-free (P = 0.001) and a significant direct association with S-ECC children (P = 0.001). Conclusions : The findings of this study demonstrated that there was an association between higher defs scores and severe early childhood caries with overweightness.

Lack of association between the G-660C polymorphism in the dopamine transporter gene (SLC6A3) and schizophrenia in the Iranian population.

Background: Dopaminergenic system plays an essential role in the plasticity of the human brain. The dopamine transporter gene (SLC6A3) mediates active reuptake of dopamine from synapsis, terminates dopamine signals, and therefore, is implicated in a number of dopamine-related disorders like psychosis. Variations in the form of single nucleotide polymorphisms in the core promoter of the SLC6A3 gene are reported to be involved in the pathogenesis of schizophrenia. In this study, we also attempted to establish the possible role of the polymorphism G-660C in the SLC6A3 gene promoter in schizophrenia in a case-control study. Materials and Methods: The allele and genotype frequency were analyzed in an Iranian cohort of 200 unrelated patients and 200 controls using polymerase chain reaction and restriction fragment length polymorphism. Results: The genotype frequency for case and control groups was GG 100%, GC 0%, CC 0%, and GG 100%, GC 0%, CC 0%, respectively. The C allele was failed in both groups. Conclusion: Our data suggest clearly that there is no association between the -660G/C polymorphism and outcome of schizophrenia in the Iranian population.

Cytogenetic abnormalities in 222 infertile men with azoospermia and oligospermia in Iran: Report and review.

Background: Infertility affects approximately 10%-15% of couples in reproductive age. In half of the couples, causes are male-related, associated with impaired spermatogenesis. There is a complex correlation between genetics and infertility. Several factors affect on gametogenesis, from which factors that lead to chromosomal abnormalities are one of the best known. The aim of this study was to determine type and rate of chromosomal abnormalities in infertile azoospermic and oligospermic males in Iranian population. Materials and Methods: The records of a total of 222 participants were evaluated retrospectively. Results: As a whole we observed 13.96% chromosomal abnormality, from which 12.15% showed numerical and 1.8% showed structural abnormalities. Conclusion: Comparison of our results with the review of the literature shows a higher incidence (4- fold) of gonosomal, in particular, numerical gonosomal, chromosomal anomalies. Cytogenetic analysis is strongly suggested for infertile men, particularly in those who suffer from azoospermia.

Taq1B polymorphism of cholesteryl ester transfer protein (CETP) gene in primary combined hyperlipidaemia.

Background & objectives: Cholesteryl ester transfer protein (CETP) gene polymorphism is known to be associated with changes in lipid profiles. Primary hyperlipidaemia is considered to be a major risk factor for pancreatitis, atherosclerosis and coronary heart disease. We investigated the association of one common polymorphism in the CETP gene (Taq1B) with plasma lipid levels and CETP activity in Iranian subjects with and without primary combined hyperlipidaemia. Methods: The study included 102 patients with primary combined hyperlipidaemia and 214 health individuals. Polymerase chain reaction and restriction fragment length polymorphisms were used for genotype detection. To determine the relationship between Taq1B polymorphism and lipid levels, lipids and CETP activity were measured in primary combined hyperlipidaemic and normolipidaemic subjects, with and without Taq1B polymorphism. Results: Plasma CETP activity was significantly (P<0.001) higher in primary combined hyperlipidaemic individuals than in controls. Plasma HDL-C was higher in both groups, in the B2B2 genotype than in the B1B1 and B1B2 genotypes, whereas the serum TG concentrations and CETP activity were lower in B2B2 genotype compared with other genotypes (B1B1 and B1B2). The genotype and allelic frequencies for this polymorphism differed significantly between hyperlipidaemic and nonmolipidaemic individuals (P<0.05). In both groups, CETP Taq 1B polymorphism (presence of B2 allele) correlated significantly with HDL-cholesterol (HDL-C) (r=0.201 and r=0.452 in control and patient groups respectively) and CETP activity (r= -0.123 for controls and r= -0.192 for patients). Interpretation & conclusions: The results showed that Taq 1B polymorphism of CETP gene was associated with changes in lipids profile and plasma CETP activity in the selected population and might have a role in contributing to genetic risk of developing coronary artery disease.

Impact of pericentric inversion of Chromosome 9 [inv (9) (p11q12)] on infertility.

BACKGROUND: One of the frequent occurrences in chromosome rearrangements is pericentric inversion of the Chromosome 9; inv (9) (p11q12), which is consider to be the variant of normal karyotype. Although it seems not to correlate with abnormal phenotypes, there have been many controversial reports indicating that it may lead to abnormal clinical conditions such as infertility. The incidence is found to be about 1.98% in the general population. MATERIALS AND METHODS: We investigated the karyotypes of 300 infertile couples (600 individuals) being referred to our infertility clinic using standard GTG banding for karyotype preparation. RESULTS: The chromosomal analysis revealed a total of 15 (2.5%) inversions, among these, 14 male patients were inversion 9 carriers (4.69%) while one female patient was affected (0.33%). The incidence of inversion 9 in male patients is significantly higher than that of normal population and even than that of female patients (P< 0.05). CONCLUSIONS: This result suggests that inversion 9 may often cause infertility in men due to spermatogenic disturbances, which are arisen by the loops or acentric fragments formed in meiosis.

Heterozygosity and allele frequencies of the two VNTRs (ApoB and D1S80) in Iranian population.

Genetic markers are used for identity testing and paternity analysis depends on knowing the allele frequencies in the population. Minisatellites show allelic variability in the number of repeat units. We have studied the allele frequencies and heterozygosity of two VNTRs (ApoB and D1S80) in Iranian populations. A total of 96 and 82 chromosomes were analyzed by PCR and gel electrophoresis for ApoB and D1S80 respectively. In the ApoB system, allele 37 was the most common followed by allele 35 whereas allele 23 was the most common followed by allele18 at the D1S80 locus. Observed heterozygosity was relatively low in ApoB than D1S80 locus, however, no significant differences were found between observed and expected heterozygosity.