Allele and Genotype Frequencies of the Polymorphic Methylenetetrahydrofolate Reductase and Lung Cancer in ther Jordanian Population: a Case Control Study.

BACKGROUND: Methylenetetrahydrofolate reductase (MTHFR) is involved in amino acid synthesis and DNA function. Two common polymorphisms are reported, C677T and A1298C, that are implicated in a number of human diseases, including cancer. OBJECTIVE: The association between MTHFR C677T and A1298C genotype and haplotype frequencies in risk for lung cancer (LC) was investigated in the Jordanian population. MATERIALS AND METHODS: A total of 98 LC cases were studied for MTHFR C677T and A1298C polymorphisms, compared to 89 controls taken from the general population, employing the PCR-RFLP technique. RESULTS: The frequency of the genotypes of MTHFR C677T among Jordanians was: CC, 59.6%, CT, 33%; and TT, 7.4% among LC cases and 49.4%, 40.2% and 10.3% among controls. No significant association was detected between genetic polymorphism at this site and LC. At MTHFR A12987C, the genotype distribution was AA, 29.5%; AC, 45.3%, and CC 25.3% among LC cases and 36.8%, 50.6% and 12.6% among controls. Carriers of the CC genotype were more likely to have LC (OR=2.5; 95%CI: 1.04-6; p=0.039) as compared to AA carriers. Smokers and males with the CC genotype were 9.9 and 6.7 times more likely to have LC, respectively (ORsmokers=9.9; 95%CI: 1.2-84.5, p=0.018; ORmen=6.6; 95%CI: 1.7-26.2, p=0.005). Haplotype analysis of MTHFR polymorphism at the two loci showed differential distribution of the CC haplotype (677C-1298C) between cases and controls. The CC haplotype was associated with an increased risk for lung cancer (OR=1.6; 95% CI: 1.03-2.4, p=0.037). CONCLUSIONS: The genetic polymorphism of MTHFR at 1298 and the CC haplotype (risk is apparently lower with the C allele at position 677) may modulate the risk for LC development among the Jordanian population. Risk associated with the 1298C allele is increased in smokers and in males. The results indicate that a critical gene involved in folate metabolism plays a modifying role in lung cancer risk, at least in the Jordanian population.

Brucellosis presenting as myelofibrosis: first case report.

We describe the case of a 29-year-old woman who presented with pancytopenia and myelofibrosis. Brucella melitensis was identified in her blood. The patient recovered completely with doxycycline and rifampin. A repeat bone marrow biopsy showed hypercellularity without myelofibrosis. Bone marrow findings in cases of pancytopenia due to brucellosis reveal normocellularity, hypercellularity, hemophagocytosis, or granuloma. To our knowledge this is the first report of brucellosis causing myelofibrosis. Brucellosis should be considered as a possible cause of myelofibrosis in endemic areas.

Thrombophilia-related genetic variations in patients with pulmonary embolism in the main teaching hospital in Jordan.

OBJECTIVE: To study the frequency of Factor V Leiden (FVL), prothrombin gene mutation G20210A and methylenetetrahydrofolate reductase C677T in patients with acute pulmonary embolism (PE); and to investigate whether these factors are more frequent in patients who have no obvious risk factors for venous thrombo-embolism compared to those with obvious risk factors. METHODS: A case-control study conducted at Jordan University Hospital, Amman, Jordan during the period 2005-2007. Compared 92 patients with acute PE to 99 normal subjects. All subjects were investigated for the 3 genetically related thrombophilic factors. RESULTS: The frequency of these factors in patients were 22/92 (23.9%) FVL, 3/92 (3.3%) Factor II (FII) and 48/92 (52.2%) methylenetetrahydrofolate reductase (MTHFR). In the control group, FVL was 12/99 (12.1%), FII 0/99 (0%), and 53/99 (53.5%) MTHFR. There was a statistically significant difference between patients and controls for FVL (p=0.03), but no statistical significance for FII (p=0.10) and MTHFR (p=0.85). In patients with no obvious risk factors, the frequency of these factors were 8/29 (27.6%) FVL, 2/29 (6.9%) FII, and 14/29 (48.3%) for MTHFR compared to patients with obvious risk factors 14/63 (22.2%) for FVL, 1/63 (1.6%) FII, and 33/63 (52.3%) MTHFR. CONCLUSION: The FVL is statistically more frequent in patients with PE compared to the control group, and the frequency of FVL, FII, and MTHFR is not significantly higher in patients with acute PE who have no obvious risk factors compared to those with obvious risk factors.

Risk stratification for venous thromboembolism in hospitalized patients in a developing country: a prospective study.

Venous Thrombo-Embolism (VTE) is a serious complication in hospitalized patients but can be preventable. This prospective study addresses risk factors assessment and the use of heparin in this population. About 2,496 non pediatric patients were admitted to Jordan University Hospital between June 12, 2007 and July 19, 2007. A random sample of 624 patients consisting of every fourth admission was chosen. The stratification of risk factors was assessed using Caprini model and the ACCP score. The mean age of the patients (229 males and 395 females) was 45.34 +/- 18.3 years. More than 80% of the admitted patients were considered at high risk for VTE but heparin was used in only 26% of the patients. The majority of our patients constitute a high-risk population. Implementation of strategies including educational sessions and risk stratification guidelines can reduce the incidence, morbidity, and mortality of VTE especially in developing countries.