The ICAM-1 469 T/C gene polymorphism but not 241 G/A is associated with Behçets disease in the Lebanese population.

OBJECTIVE: To investigate the association of the 2 intracellular adhesion molecules-1 (ICAM-1) gene polymorphisms [thymidine/cytidine (T/C) 469 and guanosine/adenosine (G/A) 241] in Behçets disease in Lebanon. METHODS: We initiated the study in July 2003, and carried out the work in the research laboratory of Beirut Arab University, Beirut, Lebanon. We extracted the DNA by glass fiber matrix mini column. We amplified the ICAM gene by polymerase chain reaction (PCR) and tested the PCR products for the presence of the polymorphisms using a restriction enzyme specific for each polymorphism. We analyzed the results by agarose electrophoresis. RESULTS: We demonstrated the association of only one single nucleotide polymorphism (SNP) (K469) with Behçets disease, while we could not detect the other SNP (G241A) in either controls or patients in the Lebanese population. CONCLUSION: The ICAM-1 gene polymorphism 469 T/C, but not 241 G/A, may encode risk for Behçets disease in the Lebanese population.

The ICAM-1 (469 T/C) gene polymorphism but not (241 G/A) is associated with Behcet`s disease in the Lebanese population.

OBJECTIVE: To investigate the association of the 2 intracellular adhesion molecules-1 (ICAM-1) gene polymorphisms [thymidine/cytidine (T/C) 469 and guanosine/adenosine (G/A) 241] in Behcet`s disease in Lebanon. METHODS: We initiated the study in July 2003, and carried out the work in the research laboratory of Beirut Arab University, Beirut, Lebanon. We extracted the DNA by glass fiber matrix mini column. We amplified the ICAM gene by polymerase chain reaction (PCR) and tested the PCR products for the presence of the polymorphisms using a restriction enzyme specific for each polymorphism. We analyzed the results by agarose electrophoresis. RESULTS: We demonstrated the association of only one single nucleotide polymorphism (SNP) (K469) with Behcet`s disease, while we could not detect the other SNP (G241A) in either controls or patients in the Lebanese population. CONCLUSION: The ICAM-1 gene polymorphism 469 T/C, but not 241 G/A, may encode risk for Behcet`s disease in the Lebanese population.

Fragrance chemicals lyral and lilial decrease viability of HaCat cells' by increasing free radical production and lowering intracellular ATP level: protection by antioxidants.

We investigate in this study the biochemical effects on cells in culture of two commonly used fragrance chemicals: lyral and lilial. Whereas both chemicals exerted a significant effect on primary keratinocyte(s), HaCat cells, no effect was obtained with any of HepG2, Hek293, Caco2, NIH3T3, and MCF7 cells. Lyral and lilial: (a) decreased the viability of HaCat cells with a 50% cell death at 100 and 60 nM respectively; (b) decreased significantly in a dose dependant manner the intracellular ATP level following 12-h of treatment; (c) inhibited complexes I and II of electron transport chain in liver sub-mitochondrial particles; and (d) increased reactive oxygen species generation that was reversed by N-acetyl cysteine and trolox and the natural antioxidant lipoic acid, without influencing the level of free and/or oxidized glutathione. Lipoic acid protected HaCat cells against the decrease in viability induced by either compound. Dehydrogenation of lyral and lilial produce α,ß-unsaturated aldehydes, that reacts with lipoic acid requiring proteins resulting in their inhibition. We propose lyral and lilial as toxic to mitochondria that have a direct effect on electron transport chain, increase ROS production, derange mitochondrial membrane potential, and decrease cellular ATP level, leading thus to cell death.

Association of MMP3-1171(5A>6A) polymorphism with lung cancer in Lebanon.

Matrix metalloproteinases (MMPs) are a family of enzymes that degrade extracellular matrix components and are involved in the development and progression of cancer. Lung cancer is the most commonly diagnosed cancer in Lebanon. This study was undertaken to investigate the association between -1171(5A>6A) polymorphism in the promoter of MMP3 gene and the susceptibility to lung cancer in a Lebanese population. The MMP3 polymorphism was investigated in 41 lung cancer patients and 51 unrelated healthy controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. We found a significant association between MMP3-1171 5A allele and lung cancer (Odds ratio [OR]=2.7, 95% [CI]=1.3-5.3; Fisher's p-value=0.005). This study may form an additional evidence for the association of MMP3 enzyme and genetic susceptibility to lung cancer.

Study of the association between -403G/A and -28C/G RANTES gene polymorphisms and asthma in Lebanon.

CONTEXT: Asthma is a complex inflammatory condition often associated with bronchial hyper reactivity and atopy. Genetic and environmental factors are implicated in the etiopathogenesis of asthma. Regulated upon Activation Normal T- cell Expressed and Secreted (RANTES) is a CC chemokine responsible for the recruitment of inflammatory cells, suggesting a possible role for this chemokine in asthma. Both -403A and -28G alleles of the RANTES promoter region were found to be associated with asthma/atopy in some but not all studies. AIM: The purpose of this study was to investigate the genetic influence of -403A and -28G alleles of the RANTES promoter region on the development of asthma in Lebanon. SETTINGS AND DESIGN: This case control study was conducted at Makassed Hospital, Beirut on 40 asthmatic patients and 38 healthy controls. METHODS: RANTES gene polymorphisms -403G/A and -28C/G alleles were genotyped using PCR-RFLP. RESULTS: No significant differences in allele or genotype frequencies for the RANTES gene polymorphisms between asthmatic patients and controls were found. The difference of the -403 GA genotype frequency between patients and controls was not statisti-cally significant; (OR=0.8, 95% CI=0.2-2.3, P=0.8). Similarly, the difference of the A-allele frequencies between patients and con-trols was not significant (OR=0.824, CI=0.3-2.2, P=0.7). CONCLUSIONS: Our data show that RANTES gene promoter polymorphisms are not associated with asthma susceptibility in the Lebanese population.

MMP1-1607(1G>2G) polymorphism and the risk of lung cancer in Lebanon.

CONTEXT: Matrix metalloproteinases (MMPs) are a family of enzymes that degrade various components of the extracellular matrix and are involved in the development and progression of cancer. Lung cancer is the most commonly diagnosed cancer in Lebanon. MMP1 is responsible for degrading stromal collagens, which enhance the ability of neoplastic cells to cross basal membrane of both the endothelium and the vascular endothelium. A recent meta-analysis has suggested that the MMP1-1607 2G allele may be associated with an increased risk for certain types of cancers. AIM: This study was undertaken to investigate the association between guanine insertion polymorphism in the MMP1 promoter and the susceptibility to lung cancer in the Lebanese population. SETTINGS AND DESIGN: This case-control study was conducted on 41 patients with lung cancer and 51 age-matched healthy controls, recruited from different regions of Lebanon. METHODS: Cases were histologically confirmed lung cancer patients obtained from different hospitals in Lebanon. Controls were healthy unrelated individuals with no history of cancer or genetic diseases. All subjects were genotyped for MMP1 -1607(1G>2G) polymorphism using polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP). RESULTS: No statistically significant differences were found when genotype and allele distribution of MMP1 -1607(1G>2G) polymorphism were compared between patients with lung cancer and controls [P= 0.6 by chi-squared test on a 3×2 contingency table; allelic P=0.61, OR (95% CI) = 1.18 (0.60-2.31)]. CONCLUSION: Our data shows that MMP1 promoter polymorphism is not associated with lung cancer susceptibility in the Lebanese population.

Association of HLA class II alleles and CTLA-4 polymorphism with type 1 diabetes.

Type-1 diabetes mellitus (T1DM) is a progressive complex autoimmune disease in which combinations of environmental as well as genetic factors contribute to T-cell mediated destruction of insulin-secreting ß-cells of the pancreas. HLA class II alleles on chromosome 6p21 [insulin dependent diabetes mellitus 1 (IDDM1)], especially DR and DQ, show strong association with T1DM. In addition, several studies have suggested that polymorphisms in the CTLA-4 gene (IDDM12) on chromosome 2q33 form part of the genetic susceptibility for type 1 diabetes. The aim of this study was to analyze HLA alleles of the DQB1 and DRB1 genes using polymerase chain reaction using sequence specific primers (PCR-SSP) technique and to investigate the association of the A49G CTLA-4 polymorphism using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis in Lebanese T1DM patients. The study was conducted on 39 Lebanese T1DM patients. Results of HLA typing showed an increased frequency of the HLA-DQB1FNx010201, HLA-DQB1FNx010302, HLA-DRB1FNx010301 and HLA-DRB1FNx010401 alleles, suggesting risk association and thus can be considered as susceptibility alleles. On the other hand, strong protection against the disease was conferred by the HLA-DRB1FNx01110101, HLA-DQB1FNx010301 and HLADQB1FNx010601 alleles. RFLP analysis of the A49G polymorphism showed a significant increase in the G allele and GG genotype frequencies in patients, suggesting that CTLA-4 may be considered as a susceptibility gene for the development of T1DM in the Lebanese population. Analysis of the two polymorphisms showed no detectable association between the two genes. However, a significant negative association of the G allele with the DQB1FNx010201 allele was observed. This might indicate that the two genetic risk factors, namely HLA and CTLA-4, act independently of each other with no additive effect.

Association between angiotensin-converting enzyme insertion/deletion genetic polymorphism and hypertension in a sample of Lebanese patients.

BACKGROUND/AIM: several studies have looked at the potential link between angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism and the risk of hypertension and have shown that the DD polymorphism may be associated with a higher prevalence of hypertension. Our objective was to assess for possible association between ACE variants and hypertension in a sample of Lebanese patients. METHODS: one hundred ninety-two Lebanese subjects were included. DNA was isolated and amplified by polymerase chain reaction. The products were identified by gel electrophoresis according to their size. RESULTS: one hundred fifteen (59.9%) patients were hypertensive and 77 (40.1%) were nonhypertensive with the following genotype frequencies: 43.4% DD, 45.2% ID, and 11.4% II compared with 35.2% DD, 51.9% ID, and 12.9% II, respectively. Age was found to be the most significant risk factor for hypertension. This was more prominent when accounting for ACE genotype; for instance, the DD genotype with age had a significantly higher odds ratio (OR = 11.852; p = 0.001) than the ID genotype with age (OR = 4.599; p = 0.006), II genotype with age (OR = 1.866; p = 0.519), and age alone (OR = 5.558; p = 0.006). CONCLUSION: our results show that the ACE I/D polymorphism is common in Lebanon, and the combinations of ACE D allele and age is associated with an increased risk of hypertension.