Screening for genetic mutations in LDLR gene with familial hypercholesterolemia patients in the Saudi population.

Familial hypercholesterolemia (FH) is caused by genetic defects involving the low density lipoprotein-receptor (LDL-R), predisposing affected people to premature atherosclerotic cardiovascular disease and death. The aim of the present study was to assess certain exons in the LDLR gene mutation detection analysis affecting in the Saudi population with FH. This case-control study was carried out with 200 subjects; 100 were FH cases and 100 were healthy controls. Five mL of venous blood samples were collected from all the subjects and used for biochemical and genetic analysis. DNA was extracted from 2 mL of the EDTA samples, and precise primers were designed for LDL-R gene which includes Exon 3, 4 and 8. PCR was followed by DNA sequencing. In our study, we found 25 mutations in cases in Exon-3 and 2 mutations in controls, however, we have found only 5 mutations in exon 4 and none of the mutations were identified in exon 8. We conclude that screening of FH among Saudi population is very important to identify individuals who are prone to develop the disease.

Autoantibody detection: prevailing practices at a tertiary care hospital in Riyadh.

BACKGROUND: Anti-nuclear antibody (ANA) test as the first level investigation for detection of auto-immune rheumatic disease has been recommended in a number of international guidelines. This study was performed to evaluate the local practice and trends of auto-antibody laboratory requests. METHODS: Data were collected from 249 initial laboratory requests for first level auto-antibody detection between April 2012 and April 2013 in the Immunology Unit at King Khalid University Hospital, Riyadh. This group of patients included 151 females and 98 males (mean age 40.1 +/- 21; range 4-85 years). RESULTS: Of the total requests, ANA as a single first level investigation was requested by only 32 (13%) clinicians whereas the rest of the investigations included simultaneous testing of ANA and second level extractable nuclear antigen (ENA) auto-antibody tests. Anti-double stranded DNA (anti-dsDNA) antibody was simultaneously tested with ANA in 158 patients as first level test where both the tests were positive in 44 (27.8%) patients and in 24 (15.1%) patients a negative ANA test was associated with a positive anti-dsDNA antibody test. Rheumatoid factor (RF) tested positive in 04/53 (7.5%), anti-neutrophil cytoplasmic antibody (ANCA) in 01/48 (2%) and SS-A and SS-B in 03/37 (8.1%) requests as first level tests with ANA. CONCLUSIONS: Using second level auto-antibody tests in conjunction with ANA as the first line investigation does not appear to be a cost effective approach, highlighting the importance of adherence to the guidelines. ANA negative and anti-dsDNA positive group of patients requires further assessment in a large scale study.

Association of angiotensin converting enzyme gene insertion/deletion polymorphism and familial hypercholesterolemia in the Saudi population.

BACKGROUND: The study of the association between genotype and phenotype is of great importance for the prediction of multiple diseases and pathophysiological conditions. The relationship between angiotensin converting enzyme (ACE) Insertion/Deletion (I/D) polymorphism and Familial Hypercholesterolemia (FH) has been not fully investigated in all the ethnicities. In this study we sought to determine the frequency of I/D polymorphism genotypes of ACE gene in Saudi patients with FH. RESULTS: This is a case-control study carried out purely in Saudi population. Genomic DNA was isolated from 128 subjects who have participated in this study. ACE gene I/D polymorphism was analyzed by polymerase chain reaction in 64 FH cases and 64 healthy controls. There was no statistically significant difference between the groups with respect to genotype distribution. Furthermore, we did not find any significant difference in the frequency of ACE I/D polymorphism in FH subjects when stratified by gender (p = 0.43). CONCLUSION: Our data suggest that ACE gene I/D polymorphism examined in this study has no role in predicting the occurrence and diagnosis of FH.

Prognostically significant fusion oncogenes in Pakistani patients with adult acute lymphoblastic leukemia and their association with disease biology and outcome.

BACKGROUND AND OBJECTIVES: Chromosomal abnormalities play an important role in genesis of acute lymphoblastic leukemia (ALL) and have prognostic implications. Five major risk stratifying fusion genes in ALL are BCR-ABL, MLL-AF4, ETV6-RUNX11, E2A-PBX1 and SIL-TAL1. This work aimed to detect common chromosomal translocations and associated fusion oncogenes in adult ALL patients and study their relationship with clinical features and treatment outcome. METHODS: We studied fusion oncogenes in 104 adult ALL patients using RT-PCR and interphase-FISH at diagnosis and their association with clinical characteristics and treatment outcome. RESULTS: Five most common fusion genes i.e. BCR-ABL (t 9; 22), TCF3-PBX1 (t 1; 19), ETV6-RUNX1 (t 12; 21), MLL-AF4 (t 4; 11) and SIL-TAL1 (Del 1p32) were found in 82/104 (79%) patients. TCF3-PBX1 fusion gene was associated with lymphadenopathy, SIL-TAL positive patients had frequent organomegaly and usually presented with a platelets count of less than 50 x10(9)/l. Survival of patients with fusion gene ETV6-RUNX1 was better when compared to patients harboring other genes. MLL-AF4 and BCR-ABL positivity characterized a subset of adult ALL patients with aggressive clinical behaviour and a poor outcome. CONCLUSIONS: This is the first study from Pakistan which investigated the frequency of 5 fusion oncogenes in adult ALL patients, and their association with clinical features, treatment response and outcome. Frequencies of some of the oncogenes were different from those reported elsewhere and they appear to be associated with distinct clinical characteristics and treatment outcome. This information will help in the prognostic stratification and risk adapted management of adult ALL patients.

Zinc and antioxidant vitamin deficiency in patients with severe sickle cell anemia.

BACKGROUND: Patients with severe sickle cell anemia (SCA) have a higher potential for oxidative damage due to chronic redox imbalance in red blood cells that often leads to hemolysis, endothelial injury and recurrent vaso-occlusive episodes. This study evaluated the plasma levels of vitamins A, C and E as indicators of antioxidant status. In addition, serum levels of zinc and copper were also estimated. PATIENTS AND METHODS: Twenty-five adult patients with severe sickle cell anemia (12 males and 13 females aged 29.72+/-12.94 years) and 25 matched controls were studied. Plasma levels of vitamins A, C and E were measured by HPLC technique. Serum zinc and copper levels were measured by atomic absorption spectrometry. RESULTS: There was a significant decrease in plasma levels of vitamins A, C and E and in serum levels of zinc in patients with SCA as compared with controls (P<0.0001). Serum copper levels were signficantly elevated compared with controls (P<0.0001). CONCLUSION: These findings emphasize the significant deficiencies of the antioxidant vitamins A, C and E and the trace element zinc along with the significant elevation of serum copper in patients with severe sickle cell disease. Further studies are needed to find out whether supplementation of antioxidant vitamins and zinc may ameliorate some sickle cell disease complications.