Transcription factor-7-like 2 gene variants are strongly associated with type 2 diabetes in Lebanese subjects.

We tested the association of TCF7L2 variants with type 2 diabetes (T2DM) in 691 Lebanese people and 919 controls. rs7901695, rs4506565, rs7903146, rs12243326, rs7895340, and rs12255372 minor allele frequencies were higher in T2DM. Haplotype analysis (rs7901695-rs4506565-rs7903146-rs12243326-rs7895340-rs11196205-rs12255372) identified positively- (2122112, 2222222) and negatively- (1111111) T2DM-associated haplotypes. TCF7L2 is a common T2DM candidate gene in Lebanese people.

Acquired and genetic risk factors for deep vein thrombosis of lower extremities among Lebanese patients.

AIM: Venous thrombosis results from the interaction of environmental and genetic risk factors. These factors vary according to the ethnic and geographic distribution of the populations. The aim of this study is to define the role of acquired and genetic risk factors for venous thrombosis of lower extremities among Lebanese patients assessed in a university hospital and to discuss them according to the international literature. MATERIAL AND METHODS: From January 2005 to January 2010, 166 patients (72 males and 94 females) were diagnosed with lower extremity deep vein thrombosis. Mean age was 67 years (range: 25 to 96 years). RESULTS: The most frequently reported acquired risk factors for venous thrombosis in this study were advanced age, obesity, history of venous thromboembolism, immobilization, surgery, varicose veins and malignancy. Screening for prothrombotic genetic abnormalities was requested in patients with conditions highly suggestive of hypercoagulation state such as young patients, patients with spontaneous, recurrent or extensive venous thrombosis, patients with family history, oral contraceptives, air travel and pregnancy. All the 45 patients (27.1%) tested for thrombophilia were positive and were carriers for factors V-Leiden (17.4%), MTHFR C 677 T (16.8%), MTHFR A 1298 C (4.8%), II G 20210 A (1.8%) and V H 1299 R (1.2%) mutation. Twelve patients (7.2%) had increased homocysteine level. CONCLUSION: Advanced age is the most common risk factor for venous thrombosis in these series. Thrombophilia is the second most frequently observed risk factor and is related to the high prevalence of factor V-Leiden and MTHFR C 677 T mutation among the Lebanese population.

Strong association of common variants in the IGF2BP2 gene with type 2 diabetes in Lebanese Arabs.

OBJECTIVE: Several genome-wide association studies and replication analyses have identified common variation at the insulin-like binding protein 2 (IGF2BP2) gene to be associated with type 2 diabetes (T2DM). The aim of this study was to replicate in a Lebanese Arab population identified associations of IGF2BP2 variants rs4402960 and rs1470579 with T2DM. METHODS: This case-control study involved 544 T2DM patients and 606 control subjects. Genotyping was done by the allelic exclusion method. RESULTS: T allele of rs440960 (P=6.5 × 10(-6)) and C allele of rs1470579 (P=5.3 × 10(-4)) were significantly associated with T2DM; both SNPs were in strong LD (D'=0.83, r(2)=0.58). While both IGF2BP2 SNPs were significantly associated with T2DM under additive and recessive models, only rs4402960 remained significantly associated with T2DM under the dominant model. Taking the common rs4402960/rs1470579 GA haplotype as reference, multivariate analysis confirmed the positive association of TC (P=0.009; OR, 1.43; 95%CI, 1.09-1.87), and TA (P<0.001; OR=5.49; 95%CI=2.09-14.39) haplotypes with increased T2DM risk. These differences remained significant after applying the Bonferroni correction for multiple testing. CONCLUSION: We validate that IGF2BP2 susceptibility variants rs4402960 and rs1470579 associate with T2DM in Lebanese Arabs.

Livedoid vasculopathy associated with combined prothrombin G20210A and factor V (Leiden) heterozygosity and MTHFR C677T homozygosity.

Livedoid vasculopathy (LV) is an occlusive thrombotic disease of lower extremities. A 34-year-old woman presented with 4-year history of recurrent necrotic and painful lesions with violaceous and purpuric border on both legs. Initial treatment with hydroxychloroquine, dapsone and prednisone were unsuccessful. Skin biopsy showed inflammatory infiltrate with epidermal necrosis. Prothrombin G20210A and factor V-Leiden heterozygosity, and MTHFR C677T homozygosity with hyperhomocysteinemia were confirmed. LV diagnosis was made; acetylsalicylic acid, folic acid, vitamin B12, and prednisone treatement resulted in complete healing. This is the first report on coexistence of prothrombin G20210A, factor V-Leiden, and homozygous MTHFR C677T with hyperhomocysteinemia in LV.

Association of selective HLA class II susceptibility-conferring and protective haplotypes with type 2 diabetes in patients from Bahrain and Lebanon.

The association of HLA class II with type 2 diabetes (T2DM) was investigated in Bahraini and Lebanese subjects. DRB1*070101 (Lebanese and Bahraini) and DQB1*0201 (Lebanese) were susceptibility-conferring alleles, and unique susceptibility-conferring/protective haplotypes were found in both patient groups. Regression analysis confirmed that DRB1*070101-DQB1*0201 (Bahraini) and DRB1*110101-DQB1*0201 (Lebanese) were susceptibility-conferring haplotypes.

Prevalence of antibodies against hepatitis B virus and hepatitis C virus among blood donors in Lebanon, 1997-2003.

The prevalence of hepatitis B virus (HBV) antigens (HBsAg) and antibody to hepatitis C virus (anti-HCV) was determined among 16,084 blood donors (14,993 males; mean age, 31.7 +/- 8.2 years and 1084 females; mean age, 31.4 +/- 8.2 years) in the period 1997-2003. Of the donors screened, 149 were HBsAg positive (0.926%), and 65 were anti-HCV positive (0.404%). There was a steady decline in HBsAg prevalence from 1.56% (1997) to 0.33% (2003) and in anti-HCV from 1.22% (1997) to 0.16% (2003). Females had a higher prevalence of anti-HCV (P = .031) and HBsAg (P = .047). Results obtained are of value in light of the occurrence of HBV and HCV transmission by nonparenteral routes.

Factor V G1691A (Leiden) and prothrombin G20210A single-nucleotide polymorphisms in type 2 diabetes mellitus.

The association of the single nucleotide polymorphisms (SNPs) G1691A in coagulation factor V (FV)-Leiden and G20210A in prothrombin (PRT) genes with type 2 diabetes mellitus (T2DM) were analyzed in 112 T2DM patients (58 males, 54 females; mean age 55.24 +/- 13.5 years) and 249 healthy control subjects (118 males, 131 females; mean age 53.03 +/- 13.8 years). No association was found for FV-Leiden with T2DM, as the frequency of the G/G (82.1% vs. 85.5%), G/A (17.0% vs. 14.1%), and A/A (0.9% vs. 0.4%) genotypes was not different between patients and controls, respectively (P = 0.644). Similarly, lack of association of PRT G20210A with T2DM was seen among the population studied, and the frequency of the G/G (92.9% vs. 97.2%), G/A (6.3% vs. 2.8%), and A/A (0.9% vs. 0.0%) genotypes was similar among patients and controls, respectively (P = 0.094). Neither FV-Leiden nor PRT G20210A was associated with, and no evidence for interactions between these mutations was seen in, T2DM.

A case control study on the contribution of factor V-Leiden, prothrombin G20210A, and MTHFR C677T mutations to the genetic susceptibility of deep venous thrombosis.

BACKGROUND: Insofar as the inherited prothrombotic single nucleotide polymorphisms (SNPs) factor V G1691A (FV-Leiden), prothrombin (PRT) G20210A, and methylenetetrahydrofolate reductase (MTHFR), C677T are inherited risk factors of venous thromboembolism (VTE), the aim of this study was to determine the prevalence of single and combined SNPs in 198 patients with documented deep venous thrombosis (DVT), and 697 control subjects, and to estimate the associated risks. METHODS: Factor V-Leiden, PRT G20210A, and MTHFR C677T were analyzed by PCR and restriction fragment length polymorphism (RFLP). RESULTS: The prevalence of the heterozygote and homozygous variants for FV-Leiden (52.02 vs. 14.78%, RR 6.28), PRT G20210A (19.2 vs. 3.6%; RR 6.38), and to a lesser extent the T/T genotype of MTHFR C677T (20.71 vs. 11.0%; RR 1.49) were higher among DVT patients vs. controls, respectively. Two or more SNPs were detected in 90 of 198 patients (45.5%) and in 60 of 697 controls (8.6%), with odds ratios of 16.754 for joint occurrence of FV-Leiden and PRT G20210A, 10.471 for FV-Leiden and MTHFR C677T, and 6.283 for PRT G20210A SNPs and MTHFR 677T/T. Logistic regression analysis showed a further increased odds for FV-Leiden in combination with PRT G20210A (85.198) or homozygous MTHFR C677T (81.133), and to a lesser extent for PRT G20210A in combination with homozygous MTHFR C677T (20.812). CONCLUSIONS: This indicates that FV-Leiden and PRT G20210A, more than MTHFR C677T, are important risk factors for DVT, and that the presence of more than one prothrombotic SNPs was associated with a significant risk of DVT.

Contribution of selective HLA-DRB1/DQB1 alleles and haplotypes to the genetic susceptibility of type 1 diabetes among Lebanese and Bahraini Arabs.

CONTEXT: Human leukocyte antigen (HLA) class II genes contribute to the genetic susceptibility of type 1 diabetes (T1D), and both susceptible and protective alleles were implicated with its pathogenesis, which varies among various ethnic/racial groups. OBJECTIVE: This study investigated the heterogeneity in HLA class II haplotypes distribution among Bahraini and Lebanese T1D patients. DESIGN: This was a cross-sectional retrospective study. SETTING: The study was conducted at primary care private and public health centers. PATIENTS AND OTHER PARTICIPANTS: Subjects comprised 126 T1D patients and 126 healthy controls from Bahrain and 78 Lebanese T1D patients and 111 control subjects. INTERVENTION(S): There were no interventions. RESULTS: Although Lebanese and Bahraini patients share DRB1*030101, DQB1*0201 as susceptible and DRB1*100101 and DQB1*030101 as protective alleles, DRB1*040101 was an additional susceptible allele in Bahraini patients, and DRB1*130701 and DQB1*050101 were additional susceptible and protective alleles in Lebanese, respectively. DRB1*030101-DQB1*0201 was susceptible, whereas DRB1*070101-DQB1*0201 and DRB1*110101-DQB1*030101 were protective haplotypes in Bahraini and Lebanese. DRB1*040101-DQB1*0302 and DRB1*040101-DQB1*050101 displayed different associations: they were protective in Lebanese but susceptible or neutral among Bahrainis. Whereas the frequency of homozygous DRB1*03011-DQB1*0201 was higher in Bahraini and to a lesser extent Lebanese patients, homozygous DRB1*110101-DQB1*030101 was significantly more frequent in Lebanese but not Bahraini controls, whereas DRB1*030101-DQB1*0201/DRB1*040101-DQB1*0201 was the major genotype among Bahraini patients but not Lebanese subjects in whom it was present at very low frequencies. CONCLUSION: In view of these differences between Bahraini and Lebanese, this demonstrates that the contribution of HLA class II to the genetic susceptibility to T1D must be evaluated with regard to specific HLA haplotypes and also ethnic origin and racial background.

Factor V G1691A, prothrombin G20210A, and methylenetetrahydrofolate reductase [MTHFR] C677T gene polymorphism in angiographically documented coronary artery disease.

BACKGROUND: Single point mutations in the genes coding for factor V [G1691A; Leiden], prothrombin [PRT; G20210A], and methylenetetrahydrofolate reductase [MTHFR, C677T] were shown to be major inherited predisposing factors for venous thromboembolism. However, their contribution in the development of coronary artery disease [CAD] remains controversial. The aim of the study was to examine the association of these mutations in CAD. METHODS: A total of 96 patients with angiographically-demonstrated CAD [mean age 55.3 +/- 11.3], and 404 healthy subjects [mean age 50.7 +/- 8.9] were recruited into the study. Fasting plasma homocysteine was determined by HPLC, and genotype analysis was assessed by PCR-RFLP. RESULTS: The carrier frequency of factor V-Leiden (14.6% vs. 15.1%, p = 0.617) and PRT G20210A (3.1% vs. 3.0%; p = 0.936) were similar between patients and controls, respectively. In contrast, the frequency of the MTHFR variant C677T was 71.9% among patients compared with 45.5% in controls (p < 0.001), of which the T/T genotype was significantly higher among patients (31.3%) than controls (4.5%; p < 0.001). Significantly higher homocysteine levels were seen among T/T genotype in both groups compared to non-T/T carriers (p < 0.05), and among patients compared with controls (18.47 +/- 3.73 micromol/L vs. 16.28 +/- 4.16 micromol/L). In addition, the coexistence of MTHFR C677T with FV-Leiden was seen in 10.4% of CAD patients compared 6.9% of controls (p = 0.001). CONCLUSION: While results from this study clearly demonstrate a strong association of hyperhomocysteinemia and homozygosity of the MTHFR C677T, but not FV-Leiden or PRT G20210A, mutations with confirmed CAD, they also suggest a potential role for factor V-Leiden in MTHFR C677T carriers.

Outbreak of Burkholderia cepacia bacteremia traced to contaminated hospital water used for dilution of an alcohol skin antiseptic.

OBJECTIVE: To identify the source of an epidemic of Burkholderia cepacia bloodstream infections during 7 years (411 episodes in 361 patients). DESIGN: Outbreak investigation. SETTING: A 250-bed university hospital in Beirut, Lebanon. METHODS: Matched case-control and retrospective cohort studies, and microbiological surveillance and polymerase chain reaction-restriction fragment length ascertainment were employed. Special media and filtration techniques were used to isolate organisms from water and diluted alcohol solutions. RESULTS: In a group of 50 randomly selected case-matched patients from 1999, the positive blood cultures were concomitant with fever in 98%, intravenous phlebitis in 44%, and recurrent bacteremia in 20%. Fever disappeared approximately 6 hours after intravenous catheter removal. Polymerase chain reaction-restriction fragment length polymorphism revealed strain homogeneity in patient, water, and alcohol isolates. Contaminated tap water had been used to dilute alcohol for skin antisepsis and for decontamination of the caps of heparin vials. Only sporadic cases directly attributable to breach of protocol were reported after single-use alcohol swabs were substituted. CONCLUSION: This is potentially the largest single-source nosocomial bloodstream infection outbreak ever reported, and the first report of an alcohol skin antiseptic contaminated by tap water as a source for nosocomial bacteremia.

Differences in the frequency of the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene among the Lebanese population.

In view of its role in precipitating mild hyperhomocysteinemia as well as being a risk factor for vascular thrombosis, we investigated the frequency of the C677T mutation of the methylenetetrahydrofolate reductase (MTHFR) gene among 589 healthy Lebanese subjects by PCR-RFLP analysis (HinfI digestion) and compared them with those of other countries of Caucasian and non-Caucasian origin. The prevalence of the mutated homozygous (T/T) and heterozygous (C/T) C677T MTHFR genotype was 11.04% and 39.73%, respectively, giving an allele frequency of 0.309. While the prevalence of the T/T genotype was similar with respect to gender, higher prevalence was noted among Christian (13.08%) compared to Moslem (7.66%) subjects (P < 0.001), and heterogeneity in its distribution was seen in the different Lebanese provinces, and was directly related to the Christian/Moslem composition of each province. The distribution of the MTHFR C677T in Lebanon is unique with regard to its higher occurrence among Christians compared to Moslems, adding to the existing body of literature on the heterogeneity of its prevalence and distribution.

Prevalence of hepatitis C virus isolate genotypes from chronically infected Lebanese patients: a hospital-based study.

To assess percentages of hepatitis C virus (HCV) genotypes in infected Lebanese patients referred to St. George Hospital, Beirut, Lebanon, 77 infected cases were studied. Of those, 27 were hemodialysis patients. Genotyping was performed by nested PCR of the HCV core-region with specific primers, followed by DNA enzyme-immunoassay using HCV type and subtype-specific probes. Single genotype infections were detected in 52 patients (67.5%). In these cases, types 1, 2, 3 and 4 were detected in 19.5%, 32.5%, 5.1% and 10.4% of the cases respectively. Twenty-five (32.5%) samples showed mixed genotype infections. Single genotype distribution was significantly different among dialysis and non-dialysis patients. In the dialysis group, genotype 2 was predominant (80%, p < 0.001). In single HCV genotype-infected patients, subtype 1b was frequently detected in nondialysis cases (34.4%) whereas this genotype was found in only 5% of dialysis cases. Genotypes 5 and 6 were not detected in any of the cases studied. This pilot hospital-based study provides evidence for the diversity of HCV genotypes in the Lebanese population and establishes differences in distribution depending on the risk group.