A középkorú lakosság morbiditásának és mortalitásának összefüggése az MHC centrális régiójában található egyes génvariánsokkal és haplotipusokkal = Relationship between the morbidity and mortality of the middle-age people with some gene variants and haplotypes in the central region of MHC

A projekt kereteben -korabbi adataink utanvizsgalat celjabol - a kozepkoru lakossag morbiditasanak es mortalitasanak osszefuggeseit tanulmanyoztuk az MHC centralis regiojaban talalhato egyes genvariansokkal es haplotipusokkal. Fontosabb uj eredmenyeink: 1. Uj modszert dolgoztunk ki a C4A es C4B genek kopiaszamanak meghatarozasara 2. A C4B*Q0 (a C4B gen alacsony kopia szama) es a fokozott cardiovascularis morbiditas es mortalitas kozott kapcsolatot sikerult megerősitenunk az uj genotipizalasi modszer segitsegevel, 3. Elsőkent sikerult felterkepezni az ősi kiterjesztett MHC haplotipusok előfordulasat a magyar populacioban es bizonyitottuk, hogy a leggyakoribb, 8.1 j. ősi haplotipus hordozoinak colorectalis carcinoma kockazata lenyegesen nagyobb, mint a nem-hordozoke. 4. A C4B*Q0 genotipus es a fokozott cardiovascularis morbiditas es mortalitas kozott osszefugges egyik lehetseges magyarazata az, hogy a 21-hidroxilaz enzimet kodolo CYP-21 gen funkcionalis rendellenessege es a C4A/C4B genszan kozotti osszefugges all fenn. Kozel 100 egyen CYP-21 genjenek szekvenalasa segitsegevel talaltunk ilyen osszefuggest: a gen 4-es intronjaban talahato ket SNP ritka allelje csak a C4B*Q0 hordozokban fordult elő. Projektunk celkitűzeseit sikerult teljesiteni, a kapott eredmenyeinket 15, rangos nemzetkozi folyoiratokban megjelent kozlemenyben publikaltuk. | In order to reexamine our previous findings we studied the possible relationship between the cardiovascular morbidity/mortality of the middle-aged people and some alleles and haplotypes encoded in the central MHC region. Main results of the project: 1. A new method was worked out for direct counting of the copy number of the C4A and C4B genes. 2. Using this new method we have supported by new findings the strong association between the low copy number of the C4B genes (C4B*Q0) and the high rate of cardiovascular morbidity and mortality. 3. We were the first to map the occurrence of the ancestral extended MHC haplotypes in the Hungarian population and found that the carriers of the so-called 8.1 ancestral haplotype have an increased risk to develop colorectal cancer. 4. One of the possible explanation of the strong correlation between the C4B*Q0 genotype and the increased cardiovascular morbidity and mortality could be an association of the functional abnormalities of the CYP-21 gene (that encodes the 21-hydroxylase enzyme) and the C4A/C4B gene counts. We have examined this possibility by sequencing the CYP-21 gene in almost 100 subjects and found that the rare alleles of two SNPs in intron 4 of the gene occurs only in the C4B*Q0 carriers. Aims of the project were satisfied, the results were published in 15 papers in high-ranked international journals.