No influence of SLC22A4 C6607T and RUNX1 G24658C genotypic variants on the circulating carnitine ester profile in patients with rheumatoid arthritis.

OBJECTIVE: In a Japanese study, the C6607T SNP mapping to intron 1 of the SLC22A4 gene encoding the OCTN1 protein was found to be associated with rheumatoid arthritis. Similarly, a G24658C transversion in intron 6 of the gene encoding the RUNX1 transcription factor that regulates OCTN1 and also likely OCTN2 expression was also found to confer susceptibility to the disease. METHODS: We investigated the prevalence of these two SNPs by RFLP analysis in a cohort of 209 Hungarian rheumatoid arthritis patients, and 217 healthy controls. Since both the OCTN1 and OCTN2 play a central role in the transmembrane transport of carnitine, we also determined the quantitative serum carnitine ester profile by ESI tandem mass spectrometry. RESULTS: No statistically significant differences were found comparing the genotype prevalence rates between the patients and the controls for either the SLC22A4 genotypes or for the RUNX1 SNPs. There was no significant difference in the serum carnitine ester profile when the rheumatoid arthritis patients were compared with the controls; furthermore, no significant difference in the carnitine esters could be detected when genotype specific subgroups of the patients and the controls were studied. CONCLUSION: Data of the current study do not confirm the universal and population independent susceptibility role of the SLC22A4 C6607T and RUNX1 G24658C variants for rheumatoid arthritis; furthermore, the data presented here show, that there are no significant carnitine-metabolism associated functional consequences of the different genotypes evidenced by the lack of detectable differences in the carnitine ester profiles.

Increased prevalence of glycoprotein IIb/IIIa Leu33Pro polymorphism in term infants with grade I intracranial haemorrhage.

The prevalence rates of the platelet glycoprotein IIb/IIIa Leu33Pro allele (PLA2), and factor V G1691A Leiden mutation were determined in 109 appropriate for gestational age neonates with grade I intraventricular haemorrhage (IVH) and in 118 IVH-free control infants. The PLA2 allele frequency was 16.4 % in the group of full-term infants with grade I IVH, while it was 9.5 % in the relevant controls (p < 0.005); there was no difference in the PLA allele frequencies on comparing the IVH affected (8.34 %) and unaffected (9.2 %) premature infants. By contrast, the factor V Leiden allele frequency was increased only in the subgroup of premature infants with grade I IVH as compared with the appropriate premature controls (9.25 % vs. 3.34 %, respectively, p < 0.005). These data suggest that besides the factor V Leiden mutation, the PLA2 allele, which has already been suggested to have a role in neonatal alloimmune thrombocytopenia and certain subtypes of adult stroke, can have significance in the development of the events of IVH.

Endothelial nitric oxide synthase gene interactions and the risk of ischaemic stroke.

OBJECTIVE: Endothelial nitric oxide synthase (eNOS), which produces NO, plays an important role in the endothelial function under a wide range of physiological conditions. eNOS exon 7 polymorphism (Glu298Asp, G894T) has been considered to influence the risk of coronary artery disease. Alone, however, it has not been shown to be a genetic risk factor for ischaemic stroke. With the assumption of additive interactions, we examined whether the eNOS G894T or eNOS 894TT genotypes in combination with the methylenetetrahydrofolate reductase 677TT (MTHFR 677TT) or angiotensin-converting enzyme (ACE) D/D genotype could contribute to acute ischaemic stroke. MATERIAL AND METHODS: The data on 407 consecutive patients with acute ischaemic stroke who had never suffered a previous stroke event were analysed. As a control group, 295 stroke and neuroimaging alteration-free Caucasian subjects were examined. With the use of the PCR technique, the eNOS G894T, eNOS 894TT, MTHFR 677TT and ACE D/D mutations, as unfavourable common genotypes were determined in the participants. Logistic regression models were used to evaluate the roles of the genotypes and their combinations in the development of ischaemic stroke. RESULTS: The MTHFR C677TT genotype combined with the eNOS G894T or eNOS 894TT genotypes occurred significantly more frequently in the subjects with ischaemic stroke (7.1%; P < 0.025) than in the control group (3.1%). The co-occurrence of the ACE D/D genotype and eNOS G894T or eNOS 894TT was calculated to be more frequent in the ischaemic stroke group (20.9%, P < 0.0001) than in the control group (5.4%). CONCLUSION: The eNOS G894T or eNOS 894TT genotypes in combination with the MTHFR 677TT or ACE D/D genotype increases the risk of ischaemic stroke.

Increased prevalence of factor V Leiden mutation in premature but not in full-term infants with grade I intracranial haemorrhage.

OBJECTIVES: In the current prospective study our aim was to analyse the distribution of the factor V Leiden (G1691A) mutation in preterm and full-term neonates with grade I intraventricular haemorrhage and in control neonates. STUDY METHOD: A group of 125 individually selected neonates with grade I intraventricular haemorrhage and 128 controls were investigated. RESULTS: The allele frequency was 7.2% in the total population of affected infants while it was 3.9% in the controls (p < 0.05); the latter corresponds to an average European allele frequency in healthy populations. When the infants were grouped as premature (<2,500 g and < or =36 weeks of gestational age) and appropriate for gestational age full-term infants the statistical analysis revealed an increased prevalence of the mutation in the premature group (10% allele frequency vs. 4.8% in the controls, p < 0.05), and a normal prevalence in the mature group (4.6 vs. 3.1%, respectively); therefore, the overall increase was due to the increase of incidence rate in preterm neonates. CONCLUSIONS: These data confirm our previous results and suggest that as the preterm and term infants differ from each other in haemorrhage susceptibility in many clinical particulars, carrying of the mutation has probably also a different impact in premature and in full-term infants with respect to the intraventricular haemorrhage.

[Mortality of breast cancer and frequency of mammography in Hungary]. / Emlórákos halálozás és mammográfiás vizsgálatok száma Magyarországon.

The Hungarian breast cancer mortality is above the European average. Because of the lack of effective primary prevention, the control has to be based on the improving results of treatment which is much more successful in the case of early detected cancers. Beyond the patients collaboration and the application of the recommended diagnostic protocols, the population based screening programs have high importance in achieving earlier diagnosis. This study aimed to describe the regional differences of mammography's application as an indicator of diagnostic and screening performance. The records of the outpatient services' reports containing the code for native X-ray examination of the breast were analysed in the period of 01/07/1998 to 30/04/2000. The age specific and the age standardised relative frequencies of mammographical examination were determined for the Hungarian counties and Budapest. The observed age specific frequency of mammography for the whole country was 17, 21, 11 and 4% for the age group of 40-49, 50-59, 60-69 and 70-74 years, respectively. The lowest observed values were 10 times smaller than the highest ones in every studied age group. The age standardised relative frequency of mammographical examination was higher than the national average in Tolna (2.52), Borsod-Abaúj-Zemplén (1.48), Zala (1.41), Baranya (1.33), and Csongrád (1.27) counties and in Budapest (1.35). The described data demonstrates that the Hungarian practice of mammography is far from acceptable considering the frequency of application. On the other hand, it was also explored that serious geographical differences exist within the country. It seems that there are providers that can achieve relative successes in diagnosing the breast cancers in as early stage as it is possible. The evaluation and utilisation of the experiences of these providers could increase the efficacy of interventions organised to improve the Hungarian epidemiological status of breast cancer.