Inherited Thrombophilia in a Lebanese Family of Four Generations: A Case Report of Recurrent Miscarriage.

INTRODUCTION: Factor V Leiden (G1691A), prothrombin (G20210A) and MTHFR (C677T) gene mutations were investigated in many studies for their association with Deep Venous Thrombosis. CASE PRESENTATION: A North Lebanese family has been examined, from an index case, a 40-year-old woman, who had a history of venous thrombosis with unexplained recurrent miscarriage. The index case was found to be heterozygous for factor V Leiden G1691A, prothrombin G20210A, and methylenetetrahydrofolate reductase C677T gene variants. Her family members were heterozygous for at least two of the three-point mutations, and multiple risk factors associated with thrombophilia were identified. CONCLUSION: Our findings emphasize the need for clarifying the utility and futility of thrombophilia testing in the era of molecular diagnostics.

rs3851179G>A in PICALM is Protective Against Alzheimer's Disease in Five Different Countries Surrounding the Mediterranean.

BACKGROUND: Alzheimer's Disease (AD) is a multifactorial disease affected by various factors including genetics. Although APOE is considered the major and strongest genetic risk factor, other genetic factors such as rs3851179G>A in PICALM have been reported despite that not being fully clear. OBJECTIVE: We first aimed to investigate the correlation between rs3851179G>A in PICALM and AD in Lebanese individuals affected with AD. Then, we further investigated its overall effect in five different populations from the Mediterranean region (Turkey, Italy, Spain, France and ours) through performing a meta-analysis. METHODS: We investigated the relationship between the rs3851179G>A and AD in 109 Lebanese individuals (54% affected with AD) using allele-specific PCR. Sanger Sequencing was also used to verify genotyping. RESULTS: Using a multiple logistic regression model adjusted for many covariates, only rs3851179G>A showed a negative correlation with AD (OR=0.28, P=0.04 and OR=0.07, P=0.01 for GA and AA, respectively). To go further, a meta-analysis was conducted using studies on 3,619 participants from five different populations that belong to countries surrounding the Mediterranean (Turkey, Italy, Spain, France and ours). The sensitivity test showed no genetic heterogeneity for rs3851179G>A in the pooled analysis (P=0.44 and I2=0%) and in each individual study (P>0.05). Using an additive model, our results showed a significant association between rs3851179G>A and AD (OR=0.91, P=0.003). The funnel plot was a symmetrical inverted funnel and no significant publication bias was found for our model (P=0.46). CONCLUSION: The rs3851179A allele in PICALM tends to have a protective factor against AD in the Mediterranean region.

APOE genotypes in Lebanon: distribution and association with hypercholesterolemia and Alzheimer's disease.

AIM: We first investigated the distribution of APOE genotypes in Lebanese general population and Alzheimer's disease study (ADS) groups, and compared it with 1000 genomes populations. Then, we assessed eventual association between APOE genotypes, hypercholesterolemia and Alzheimer's disease (AD). MATERIALS & METHODS: This cross-sectional study was conducted on 591 individuals. Clinical and biological data were collected, DNA was extracted and genotyped using Kompetitive allele specific PCR (KASP™) and PCR-restriction fragment length polymorphis (PCR-RFLP). Results: Prevalence of APOE genotypes in Lebanon was similar to that seen in Asian populations. APOE genotypes were not associated with hypercholesterolemia. A significant difference between APOE genotypes in AD cases versus controls and versus Lebanese general population was seen. Moreover, E4 allele was approximately threefold higher in Alzheimer's disease study patients when compared with the remaining individuals. CONCLUSION: We established the distribution of APOE genotypes in the Lebanon and showed that in contrast to lipid profile, E4 correlates with AD.

Different evolutionary histories of the coagulation factor VII gene in human populations?

Immoderate blood clotting constitutes a risk factor for cardiovascular disease in modern industrialised societies, but is believed to have conferred a survival advantage, i.e. faster recovery from bleeding, on our ancestors. Here, we investigate the evolutionary history of the Coagulation Factor VII gene (F7) by analysing five cardiovascular-risk-associated mutations from the F7 promoter and nine neutral polymorphisms (six SNPs and three microsatellites) from the flanking region in 16 populations from the broader Mediterranean region, South Saharan Africa and Bolivia (687 individuals in total). Population differentiation and selection tests were performed and linkage disequilibrium patterns were investigated. In all samples, no linkage disequilibrium between adjacent F7 promoter mutations -402 and -401 was observed. No selection signals were detected in any of the samples from the broader Mediterranean region and South Saharan Africa, while some of the data suggested a potential signal of positive selection for the F7 promoter in the Native American samples from Bolivia. In conclusion, our data suggest, although do not prove, different evolutionary histories in the F7 promoter region between Mediterraneans and Amerindians.

Population relationships in the Mediterranean revealed by autosomal genetic data (Alu and Alu/STR compound systems).

The variation of 18 Alu polymorphisms and 3 linked STRs was determined in 1,831 individuals from 15 Mediterranean populations to analyze the relationships between human groups in this geographical region and provide a complementary perspective to information from studies based on uniparental markers. Patterns of population diversity revealed by the two kinds of markers examined were different from one another, likely in relation to their different mutation rates. Therefore, while the Alu biallelic variation underlies general heterogeneity throughout the whole Mediterranean region, the combined use of Alu and STR points to a considerable genetic differentiation between the two Mediterranean shores, presumably strengthened by a considerable sub-Saharan African genetic contribution in North Africa (around 13% calculated from Alu markers). Gene flow analysis confirms the permeability of the Sahara to human passage along with the existence of trans-Mediterranean interchanges. Two specific Alu/STR combinations-CD4 110(-) and DM 107(-)-detected in all North African samples, the Iberian Peninsula, Greece, Turkey, and some Mediterranean islands suggest an ancient genetic background of current Mediterranean peoples.

Bibliometric analyses of biomedical research outputs in Lebanon and the United Arab Emirates (1988-2007).

OBJECTIVE: We assessed the role of bibliometric methods in representing quantitative and qualitative differences in biomedical research outputs in Lebanon and the United Arab Emirates (UAE). METHODS: Data on biomedical research productivity for years 1988-2007 were obtained from PubMed then imported into a specifically designed local database system and normalized to the population size for each country. RESULTS: Data reveal a continuous increase in research production in Lebanon, whereas a plateau phase is observed in the UAE between 1998 and 2007. In Lebanon, most of the citations originated from the capital city of Beirut, mainly the American University of Beirut. Detailed analysis of biomedical research objectives in Lebanon indicate a focus on internal medicine, anesthesiology, surgery, transplantation, medical genetics, pediatrics, obstetrics, neoplasms, and pain management. In the UAE, most of the biomedical publications originate from Al-Ain University. Detailed analysis of biomedical research objectives in the UAE indicate developed interest in pediatrics, obstetrics, clinical dysmorphologies, transplantation, dermatology, diabetes, and consanguinity. CONCLUSION: Biomedical research outputs quickly recovered in Lebanon following a long war (1974-1992) mainly supported by uninterrupted activities in private higher education institutes. In the UAE, the plateau phase for biomedical research output size could be due to the limitation of most of the research in the country to Al-Ain University. This situation may only improve when other institutes offering biomedical programs engage also in research activities.

Clinicopathological and genetic study of early-onset demyelinating neuropathy.

Autosomal recessive demyelinating Charcot-Marie-Tooth disease (CMT4), Dejerine-Sottas disease and congenital hypomyelinating neuropathy are variants of hereditary demyelinating neuropathy of infancy, a genetically heterogeneous group of disorders. To explore the spectrum of early-onset demyelinating neuropathies further, we studied the clinicopathological and genetic aspects of 20 patients born to unaffected parents. In 19 families out of 20, consanguinity between the parents or presence of an affected sib suggested autosomal recessive transmission. Screening of various genes known to be involved in CMT4 revealed six mutations of which five are novel. Four of these novel mutations occurred in the homozygous state and include: one in GDAP1, one in MTMR2, one in PRX and one in KIAA1985. One patient was heterozygous for a novel MTMR2 mutation and still another was homozygous for the founder mutation, R148X, in NDRG1. All patients tested negative for mutations in EGR2. Histopathological examination of nerve biopsy specimens showed a severe, chronic demyelinating neuropathy, with onion bulb formation, extensive demyelination of isolated fibres and axon loss. We did not discern a specific pattern of histopathology that could be correlated to mutations in a particular gene.