臨床および医療ゲノミクスジャーナル

Henna derived from the dried crushed leaves of the henna plant-Lawsonia inermis Linn- used commonly in ceremonial and social events throughout the Asia, Middle East and Africa that contain an active dye ingredient lawsone. Like other ortho-substituted 1,4-naphthaoquinone, lawsone induce oxidative injury to red blood cells, that could be fatal in G6PD deficient infants and rarely in children and adults. We report a previously undiagnosed G6PD deficient Arabian baby with life threatening haemolysis after topical application of henna.

Vitamin D is known to have antiproliferative, antioxidant and immunosuppressive effect and has known association with diabetes risk. Vitamin D acts through its receptor, the Vitamin D Receptor (VDR). VDR has many Single Nucleotide Polymorphisms (SNPs) of which Apa I and Taq I have been widely studied. The present study is based on correlation of VDR gene polymorphisms with diabetes patients from Southern Punjab, Pakistan. A sum
of 250 samples comprising normal controls (100) and diabetes patients (150) was collected from different areas of South Punjab, Pakistan. All of the samples were genotyped for VDR genotypes at allelic positions of rs7975232 (Apa I) and rs731236 (Taq I). Allelic frequencies were not different between controls and patients. Statistical correlation was insignificant between control and diabetics. Enrolled subjects were assayed for biochemical parameters and the results were evaluated for statistical correlation with TaqI, ApaI and with diabetes. Random Blood Sugar (RBS) showed a very strong positive correlation with glycated hemoglobin (HBA1C). In conclusion, our study showed a non-significant correlation of Apa I, Taq I with type-2 diabetes.

Background and Objectives: Vitamin D Receptor (VDR) gene polymorphism has long been known for its association with Chronic Kidney Disease (CKD). We aimed to investigate the potential role of VDR gene polymorphisms in CKD patients. 
Design and Methods: The association of VDR gene polymorphisms in CKD patients (N=147; males =100 (68.03%) and females=47 (31.97%)) is investigated in this study. The patient samples were compared with healthy control subjects (N=210; males: 130 (61.90%) and females: 80  38.10%)). Genotyping was carried out by polymerase chain reaction–restriction fragment length polymorphism method (PCR_RFLP). All the tatistical analysis was carried out using the SPSS and PLINK-software. 
Results: A significant difference in the genotype frequency of ApaI-“CC” (p=0.015, OR=0.51, 95% CI=0.29–0.91) was observed in the patients vs. control subjects. Further, we observed that individuals with a/T haplotype were at a risk (0.25-fold higher; 95% CI=0.09–0.67). The serum calcium levels were increase in the patients with ApaI (AC+CC) variants, but were significantly decreased in the AA variant (9.6 ± 1.16 vs. 9.07 ± 0.85 mg/dL, p=0.0005). The serum Hb levels were also increase in the patients with TaqI (TT) variants, but were significantly decreased in the (TC+CC) variants (8.36 ± 2.41 vs. 7.86 ± 2.20 mg/dL, p=0.03). We also observed that the “AC” genotype of the ApaI polymorphism when present in a combination with the “TC” genotype of TaqI polymorphism conferred a 1.4 times higher risk (38/54) for developing CKD using MDR analysis.
Interpretations and Conclusions: ApaI gene polymorphism of the VDR gene is significantly associated with CKD patients and the ApaI “CC” variant could be a risk allele for CKD patients in South Indian population.

Next-generation Sequencing (NGS) of tumor biopsies of both solid tumors, as well as hematological malignancies, using commercially available platforms has broadly entered routine clinical practice in medical oncology. This molecular diagnostic approach is now used mainly to test for predictive biomarkers for patients with no available further standard therapies, as diagnostics rely on genomic testing of molecular alterations to enable effective cancer treatment. However, the high cost of large multigenic panels and especially the sequencing of the entire tumor exome is a concern, especially in a developing country such as Brazil. Here we report the clinical application of a panel of 57 genes that we call ONCOTARGET (ONCOALVO) which is based on the Thermo Fisher Oncomine Focus Assay, an integrated, commercially available NGS assay for the rapid and simultaneous detection of single nucleotide variants, short insertions and deletions, copy number variations, and gene rearrangements in 52 cancer genes with therapeutic relevance, but with the addition of 5 additional genes: the Homologous Recombination Repair (HRR) genes BCRA1, BRCA2, ATM and CHEK2 that determine tumor sensitivity to inhibitors of the PARP enzyme and also KDR, which determines sensitivity to regorafenib. Twenty-five diagnostic samples of formalin-fixed, paraffin-embedded material submitted for molecular testing over a 8-month time period were analyzed so far. All patients had advanced solid tumors already refractory to conventional systemic therapy. Libraries were prepared from isolated nucleic acids and sequenced on the Ion Torrent S5 sequencer. Sequencing datasets were analyzed using the Ion Reporter software. From the samples of the 39 patients tested, we found 30 potential therapy target pathogenic gene aberrations in 22 (56.4%) patients: KRAS-7 (23.3%), BRCA1-6 (20%), BRCA2-5 (16.6%), PIK3CA-3 (10%), MAP2K1-2 (6.6%), BRAF-V600E-2 (6.6%) mutations; and also one of each: ERBB2 (3.3%), mTOR (3.3%), KIT (3.3%), ALK (3.3%) mutations and one (3,3%) CCND1 amplification. In 3 (7.69%) patients there were double mutations: BRCA1 and BRCA2 in 2 cases and BRCA2 and KRAS and one case. The Oncotarget workflow enabled a turnaround of 18½ days. Taken together, ONCOTARGET was found to be a convenient tool for fast, reliable, broadly applicable and cost-effective targeted NGS of tumor samples in routine diagnostics and therapeutic decisions with a potential to become an important asset for precision oncology in Brazil.