Genetic analysis of TMPRSS6 gene in Saudi female patients with iron deficiency anemia.

OBJECTIVE/BACKGROUND: Mutations in transmembrane protease serine 6 (TMPRSS6) gene induce high hepcidin level, which causes iron-refractory iron deficiency anemia (IRIDA) by preventing duodenal iron absorption. This study aims to identify the common genetic variations of the TMPRSS6 gene that affect iron levels among Saudi female patients with iron deficiency anemia (IDA). METHODS: All study participants were Saudi females (12-49 years old): 32 patients with IDA, 32 patients with IRIDA, and 34 healthy individuals comprising the control group. Hematological investigations, iron profile, serum hepcidin level, and TMPRSS6 gene transcription were determined. The TMPRSS6 gene was amplified, sequenced, and analyzed among all study participants. RESULTS: The mean hepcidin and TMPRSS6 RNA transcription levels in IDA and IRIDA groups were significantly lower than those in the control group. TMPRSS6 gene sequence analysis detected 41 variants: two in the 5' untranslated region (5'UTR), 17 in introns, and 22 in exons. Thirty-three variants were previously reported in the Single Nucleotide Polymorphism Database, and eight variants were novel; one novel variant was in 5'UTR (g.-2 T > G); five novel variants were detected in exons (p.W73X, p.D479N, p.E523K, p.L674L, and p.I799I). At the time of the sequence analysis of our samples, two variants-p.D479N and p.674L-were novel. However, these variants are present at a very low allele frequency in other populations (L674L, 0.00007761 and D479N, 0.000003980). CONCLUSION: This is the first study to investigate the genetic variants of TMPRSS6 gene in Saudi female patients with IDA. The generated data will serve as a reference for future studies on IDA in the Arab population.

Distinct HLA class I and II genotypes and haplotypes are associated with multiple sclerosis in Bahrain.

Multiple sclerosis (MS) has become prevalent in the Arabian Gulf area with high incidence in Bahrain due to environmental influences and genetic susceptibilities, but there is a lack of study into human leukocyte antigen (HLA) types in patients with MS in Bahrain. The present study aimed to study the HLA types expressed in MS patients compared with in control subjects. Blood samples from 50 Bahraini patients with MS and 50 Bahraini control subjects' were subjected to HLA tissue typing by polymerase chain reaction using sequence-specific primers. In comparison with those in control subjects, the allele frequencies of HLA class-I antigens A2, A9, A19, B5, B35 and B40 were higher in MS patients. For class II antigens, the allele frequencies of DR3, DR4 and DR16 were higher in MS patients. The allele frequency of DR15 was lower in MS patients than in control subjects but the difference was not statistically significant (P=0.138). The higher prevalence of the HLA-ABDR allele was common among the female patients with MS, in relapse remission stage, in cases with higher expanded disability status scale scores and with disease duration between 4 and 9 years. Haplotype HLA-A2-B40-DR2 exhibited significantly higher frequency in MS patients compared with in control subjects (P=0.03). In conclusion, the results indicated different alleles associated with MS compared with previous reviews. The present study supports the importance of identifying genetic susceptibilities and targets for therapies in specific populations and individuals, to personalize disease management in terms of prediction, protective measures and treatment.

Interleukin 1 receptor antagonist and 2'-5'-oligoadenylate synthetase-like molecules as novel biomarkers for multiple sclerosis patients in Bahrain.

BACKGROUND: Multiple sclerosis (MS) is a multi-factorial disease of the Central Nervous System (CNS) affecting young adults leading to significant disabilities over time. MS is now believed to be prevalent in Arabian Gulf area with high incidence due to environmental factors and unknown genetic variations. The objectives of this study was to detect up-regulated potential genes that might be involved in neuroinflammatory process in MS patients in Bahrain and to measure the protein levels of the expressed genes. METHODS: A microarray was used to investigate mRNA expression from 12 MS patients and 12 control subjects in Bahrain where the mRNA came from peripheral blood leukocytes. Also, 80 MS patients and 80 control subjects were analyzed to measure serum protein levels of the expressed genes by ELISA. RESULTS: The data showed 15,480 genes expressed from over 47,000 transcripts and variants. Only 5 genes were significantly up-regulated in MS patients vs control subjects; namely TNF-AIP6, IL-1RA, OASL, CLC and DOCK4 (p < 0.05). Conversely, KIAA0125 gene was significantly down-regulated (p < 0.0003). Analysis of the effector molecules of the up-regulated genes revealed that 83 MS patients had positive serum level of OASL, 87 MS patients had positive serum levels of IL-1RA, and none of the 88 MS patients showed detectable serum levels of TNF-AIP6, CLC or DOCK4. CONCLUSIONS: OASL and IL-1RA genes were strongly expressed in MS patients and that their effector molecules may be considered as biomarkers associated with the inflammatory process of the disease and possibly treatment response.