Physiological studies in animals and human support an important role of circadian system in reproduction. The aim of this study was to investigate the potential association of CLOCK gene ...polymorphisms with idiopathic recurrent spontaneous abortion (IRSA). We performed a case-control study. The study group consisted of 268 women with a history of three or more idiopathic recurrent spontaneous abortions and 284 women with at least two live births and no history of pathologic pregnancies all from Slovenia and Serbia. Two SNPs in the CLOCK gene were chosen and genotyped. The results showed a statistically significant difference in genotype distribution between the two groups in the CLOCK gene for rs6850524 and rs11932595. Our analysis showed that G allele under dominant model (GG+GC/CC) for rs6850524 (p = 2∙10-4, OR = 2.28, 95%CI = 1.46-3.56) as well as G allele under dominant model (GA+AA/AA) for rs11932595 (p = 0.04, OR = 1.47, 95%CI = 1.01-2.04) might be risk factors against IRSA. Our data suggest that genetic variability in the CLOCK gene is associated with IRSA warranting further confirmation and mechanistic investigations.
We investigated the effect of the functional insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene on the response to interferon-β (IFN-β) therapy in Croatian and ...Slovenian patients with multiple sclerosis (MS). A total of 275 IFN-β treated MS patients 162 responders (Rs) and 113 nonresponders (NRs) were genotyped by PCR. The ACE I/D genotype distribution and allele frequencies did not differ between female Rs and NRs. However, male NRs tended to have a greater prevalence of the DD genotype (P=0.073; odds ratio: 2.64; 95% confidence interval: 0.91-7.60) and a significantly higher frequency of the D allele (P=0.022; odds ratio: 2.43; 95% confidence interval: 1.13-5.20) than male Rs. Multiple forward stepwise regression analysis indicated that the negative response to IFN-β therapy was associated with the ACE-DD genotype in men (β=0.371; multiple R change: 0.132; P=0.009) and a higher pretreatment relapse rate in both men (β=-0.438; multiple R change: 0.135; P=0.015) and women (β=-0.208; multiple R change: 0.042; P=0.034). The ACE I/D polymorphism and pretreatment relapse rate accounted for ∼26.7% of the IFN-β response variability among the men in the sample. Further studies of a larger number of MS patients from different populations are necessary to evaluate these preliminary findings.
Previous studies show altered activities of matrix metalloproteinase (MMP)-2 and MMP-9 in serum and cerebrospinal fluid of multiple sclerosis (MS) and neuromyelitis optica (NMO) patients. Optic ...neuritis (ON) is a common symptom of both disorders. Here we investigated the impacts of MMP-2 −1575G/A and MMP-9 −1562 C/T gene polymorphisms on disease phenotype in 100 MS patients with ON as a first symptom and 376 MS patients with other initial symptomatology. The MMP-2 −1575G/A polymorphism led to a 5-year-earlier age of disease onset in MS patients with ON as a first symptom (p=0.009).
•MMP-2 and MMP-9 polymorphisms were evaluated in patients with and without ON at MS onset.•SNPs within MMP2 and MMP9 are not associated with ON risk or disease severity in MS patients.•MMP-2 −1575G/A polymorphism led to a 5-year-earlier MS onset among patients with ON.
Abstract Previous studies show altered activities of matrix metalloproteinase (MMP)-2 and MMP-9 in serum and cerebrospinal fluid of multiple sclerosis (MS) and neuromyelitis optica (NMO) patients. ...Optic neuritis (ON) is a common symptom of both disorders. Here we investigated the impacts of MMP-2 − 1575 G/A and MMP-9 − 1562 C/T gene polymorphisms on disease phenotype in 100 MS patients with ON as a first symptom and 376 MS patients with other initial symptomatology. The MMP-2 − 1575 G/A polymorphism led to a 5-year-earlier age of disease onset in MS patients with ON as a first symptom (p = 0.009).
Bovina spongiformna encefalopatija (BSE) je prionska bolest goveda, koja se pojavila 1985. godine u Velikoj Britaniji i izazvala veliku epidemiju izrokovanu hranom. Oboljelo je više od milijun ...životinja. Bolest se širila izvozom britanskih prehrambenih proizvoda za goveda (mesno i koštano brašno), najviše u europske zemlje, zatim Kanadu, Sjedinjene Američke Države i Japan. BSE je prenosiva na ljude konzumacijom inficiranog mesa; više od 160 slućajeva ove »varijante« Creutzfeldt-Jacobove bolesti je bila potvrđena u Velikoj Britaniji, 26 u Francuskoj i rijetki slučajevi u drugim zemljama. Konatalna infekcija u potomaka inficiranih goveda se javlja u nekih 10 %. Mlijeko je od ogromne važnosti u ljudskoj prehrani, osobito djece, a infektivnost mlijeka u ovom času još nije sasvim jasna, i premda je malo vjerojatna, ipak najnovija istraživanja pokazuju, da je moguća u određenim uvjetima, i stoga su potrebna dalja istraživanja, te epidemiološke mjere za izolaciju mogućih rizičnih životinja. Za jednu drugu sličnu prionsku bolest, a to je scrapie, infektivnost mlijeka je dokazana. Situacija na svjetskom tržištu mlijeka je danas kaotična i zahtijevala bi usku suradnju odgovornih političara i ekonomista, uz stručni nadzor veterinara i liječnika u svijetu i u Hrvatskoj.
Background. Previous studies have shown impaired fibrinolysis in multiple sclerosis (MS) and implicated extracellular proteolytic enzymes as important factors in demyelinating neuroinflammatory ...disorders. Tissue-type plasminogen activator (t-PA) and its inhibitor (PAI-1) are key molecules in both fibrinolysis and extracellular proteolysis. In the present study, an association of the TPA Alu I/D and PAI-1 4G/5G polymorphisms with MS was analyzed within the Genomic Network for Multiple Sclerosis (GENoMS). Methods. The GENoMS includes four populations (Croatian, Slovenian, Serbian, and Bosnian and Herzegovinian) sharing the same geographic location and a similar ethnic background. A total of 885 patients and 656 ethnically matched healthy blood donors with no history of MS in their families were genotyped using PCR-RFLP. Results. TPA DD homozygosity was protective (OR = 0.79, 95% CI 0.63–0.99, P=0.037) and PAI 5G5G was a risk factor for MS (OR = 1.30, 95% CI 1.01–1.66, P=0.038). A significant effect of the genotype/carrier combination was detected in 5G5G/I carriers (OR = 1.39 95% CI 1.06–1.82, P=0.017). Conclusions. We found a significantly harmful effect of the combination of the PAI-1 5G/5G genotype and TPA I allele on MS susceptibility, which indicates the importance of gene-gene interactions in complex diseases such as MS.
Objective
Blood‐borne angiotensin II is generated from angiotensinogen via cleavage by renin and angiotensin‐converting enzyme (ACE), an enzymatic cascade known as the renin–angiotensin system (RAS). ...Several lines of evidence indicate that ACE, beyond its classical role of mediating blood pressure regulation, might contribute to the etiology of substance addictions by influencing dopaminergic signaling. A functional insertion/deletion (I/D) polymorphism of the ACE gene was associated with risk for being a smoker among individuals with depression and with smoking severity in studies comprising patients with depression and healthy controls. Several reports have described significantly increased ACE activity in cerebrospinal fluid and serum among MS patients. Furthermore, in our previous work with MS patients from Croatian and Slovenian populations, we demonstrated that the ACE‐I/D polymorphism contributes to an elevated MS risk among male patients. Here we investigated whether the ACE‐I/D polymorphism might influence smoking behavior among patients with MS.
Patients and Methods
Genotyping was performed in 521 patients (males/females: 139/382) using polymerase chain reaction.
Results
We revealed no significant differences in ACE genotype and allele frequencies between smokers and nonsmokers and no significant association between the ACE‐I/D polymorphism and either pack‐year smoking history or number of cigarettes smoked daily (p > .05, respectively).
Conclusion
The ACE‐I/D polymorphism does not contribute either to risk for nicotine dependence or to smoking severity among MS patients. In the context of reports on the ACE‐I/D polymorphism and nicotine dependence among healthy controls and patients with depression, we may speculate that the mechanism by which this polymorphism influences nicotine dependence risk differs in MS compared to depression, although not compared to a healthy population. In addition to angiotensin II, other potential ACE substrates, such as substance P and neurotensin, which also influence dopaminergic neurotransmission (and are proposed to be associated with MS), may deserve study in future.
Although the detrimental effects of smoking in multiple sclerosis (MS) are well established and genetics has been proposed to play a substantial role in vulnerability to smoking, no studies have elucidated the etiology of nicotine dependence in MS. Several lines of evidence suggest that angiotensin‐converting enzyme (ACE), beyond its classical role of mediating blood pressure regulation, might contribute to the etiology of substance addictions by influencing dopaminergic signaling. We investigated whether the functional insertion/deletion (I/D) polymorphism of the ACE gene, which has previously proved to be relevant in both nicotine dependence and MS, might be associated with smoking behavior among 521 Croatian and Slovenian patients with MS. Our results indicate that the ACE‐I/D polymorphism does not contribute to the risk of developing nicotine dependence or to smoking severity among MS patients. Furthermore, in the context of reports on the ACE‐I/D polymorphism and nicotine dependence among healthy controls and patients with depression, the mechanism by which this polymorphism influences nicotine dependence risk may differ in MS compared to depression, although possibly not compared to a healthy population
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