Association of interleukin-6 (rs1800796) but not transforming growth factor beta 1 (rs1800469) with serum calcium levels in osteoporotic patients.

BACKGROUND: Osteoporosis is a multifactorial disease with a strong genetic influence. Recent studies have demonstrated that cytokines, such as TGF-ß1 and interleukin 6 (IL-6) play complex roles in the normal bone metabolism and pathophysiology of osteoporosis. Here, we investigated the roles of 2 polymorphisms mapping to the promoters of TGF-ß1and IL-6 genes on the genetic susceptibility to osteoporosis as well as calcium and vitamin D levels. METHODS: A cohort of 297 elderly participants in northern Iran comprising 181 osteoporotic patients (mean age ±â€¯SD, 68.36 ±â€¯7.21 years) and 116 unrelated healthy controls (mean age ±â€¯SD, 64 ±â€¯5.44 years) was studied for TGF-ß1(C-509T) and IL-6 (G-634C) polymorphisms using PCR-RFLP method. RESULTS: A significant relationship was observed between calcium level and IL-6 genotypes in osteoporotic males (P = 0.011) and females (P = 0.020). No significant differences were observed between osteoporotic and control groups with respect to allele frequency or genotype distribution based on the 2 selected polymorphisms under different genetic models. The results remained the same after comparing the BMD values of either the femur neck or lumbar spine with the genotypes of the elderly men and women when analyzed separately. CONCLUSION: IL-6 genotype influences serum calcium levels in osteoporotic patients. The lack of association between the common genetic variations of TGF-ß1 and IL-6 genes, and BMD highlights the complex genetic background of osteoporosis in the north of Iran.

Coinheritance of Sicilian (뫧)0-Thalassemia and Two Rare Hemoglobin Variants: A Complex Case of Hemoglobinopathy.

α-Thalassemia (α-thal) is considered as the most common inherited hemoglobin disorder worldwide. The present study describes the first observation of a combination of rare α-chain variants, and ß-globin gene cluster deletion. A 21-year-old woman with thalassemia trait, marked microcytosis, mild anemia, and normal range of Hb F was referred to Amirkola genetic center in the North of Iran for routine molecular test of thalassemia in the context of carrier detection and prevention of thalassemia major birth. Nucleotide sequencing revealed a novel compound heterozygosity status for two non-deletional mutations on HBA2, Hb O Indonesia (α116(GH4)Glu â†’ Lys), and Hb Matsue-Oki (α75 (EF4) Asp â†’ Asn), together with heterozygosity for the sicilian (δß)0-thal mutation. This finding highlights the necessity of deep molecular investigation of thalassemia in regions where thalassemia is abundant, and present highly heterogeneous population.

A Clinical and Molecular Genetic Study of 50 Families with Autosomal Recessive Parkinsonism Revealed Known and Novel Gene Mutations.

In this study, the role of known Parkinson's disease (PD) genes was examined in families with autosomal recessive (AR) parkinsonism to assist with the differential diagnosis of PD. Some families without mutations in known genes were also subject to whole genome sequencing with the objective to identify novel parkinsonism-related genes. Families were selected from 4000 clinical files of patients with PD or parkinsonism. AR inheritance pattern, consanguinity, and a minimum of two affected individuals per family were used as inclusion criteria. For disease gene/mutation identification, multiplex ligation-dependent probe amplification, quantitative PCR, linkage, and Sanger and whole genome sequencing assays were carried out. A total of 116 patients (50 families) were examined. Fifty-four patients (46.55%; 22 families) were found to carry pathogenic mutations in known genes while a novel gene, not previously associated with parkinsonism, was found mutated in a single family (2 patients). Pathogenic mutations, including missense, nonsense, frameshift, and exon rearrangements, were found in Parkin, PINK1, DJ-1, SYNJ1, and VAC14 genes. In conclusion, variable phenotypic expressivity was seen across all families.

A Comprehensive Molecular Investigation of α-Thalassemia in an Iranian Cohort from Different Provinces of North Iran.

α-Thalassemia (α-thal) is the most common monogenic disease that is caused by the absence or reduced expression of α-globin genes. The aim of this study was to investigate common α-globin mutations and their associated haplotypes in four northern provinces of Iran (Gilan, Mazandaran, Golestan, Khorasan). One thousand, one hundred and ninety-one persons were tested for α-thal mutations by gap-polymerase chain reaction (PCR), reverse dot-blot hybridization, restriction fragment length polymorphism (RFLP) analysis and sequencing. Of the nine different mutations found, the most frequent were -α3.7 (rightward deletion) (45.6%), polyadenylation site (αp°lyA2α) (α2) (AATAAA>AATGAA; HBA2: c.*92 A>G) (15.27%), - -MED (Mediterranean deletion) (6.86%), -α4.2 (leftward deletion), (6.17%), αCSα [Hb Constant Spring (Hb CS) (HBA2: c.427 T>C)] (4.62%), -α-5 nt (HBA2: c.95+2_95+6delTGAGG) (3.70%). All chromosomes bearing an α-globin point mutation [αp°lyA2α, -α-5 ntα, αCSα, αp°lyA1α (AATAAA> AATAAG; HBA2: c.*94 A>G)] showed only one haplotype that was present in most normal chromosomes, while the -α3.7 deletion was associated with three distinct haplotypes. Our results indicate that α-thal mutations are heterogeneous and -α3.7 and αp°lyA2α are the most prevalent mutations in this region. The presence of -α3.7 with three different haplotypes suggests an older history for this mutation. The high prevalence of αp°lyA2α in Mazandaran Province, Iran compared to other parts of the country and the world, suggests a founder effect. Altogether, we here provide further data confirming the heterogeneity of the northern population of Iran. These data may contribute to the establishment of a national mutation database, more accurate genetic counseling and prenatal diagnosis (PND).

The analysis of association between SNCA, HUSEYO and CSMD1 gene variants and Parkinson's disease in Iranian population.

Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder. Both genetic and environmental factors are involved in the etiology of the disease. Many studies have revealed the susceptibility genes and variations for PD which need further confirmation. Here we evaluated the association of variations in SNCA, HUSEYO and CSMD1 genes with PD. A case-control study was conducted with 489 PD patients and 489 healthy controls. DNA was extracted from peripheral blood of all subjects and rs356220 and rs11931074 in SNCA, rs2338971 in HUSEYO and rs12681349 in CSMD1 were genotyped using PCR-RFLP method. The genotypes and allele frequencies were significantly different between case and control groups for rs356220, rs11931074 and rs2338971 but not for rs12681349. We provided further evidence that rs356220 is associated with increased risk of PD supporting previous studies in Caucasian-based and Japanese populations. The association of rs11931074 with decreased risk of PD was also significant. This study revealed the first evidence of the association of rs2338971 with increased risk of PD in the Iranian population. Nevertheless, these findings need further validation via more replication studies.