IgA nefropatili hastalarda glikozilasyon bozukluğunda C1GALT1 ve ST6GALNAC2 genlerinin önemi
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Tarih
2015
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Ege Üniversitesi, Fen Bilimleri Enstitüsü
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
IgA Nefropatisi poligenik bir hastalıktır. Son zamanlarda artan kanıtlar, anormal glikozilasyon sonucu IgA1'de oluşan α2,6 sialik asit ve galaktoz bozukluğunun IgAN'nin patogenezinde rol oynadığını göstermektedir. Bu çalışmada IgA1 molekülünün glikozilasyonuna katılan üç önemli genin ST6GALNAC2, C1GALT1 ve NEU1 polimorfizmlerinin IgAN ile ilişkisi araştırılmıştır. Histolojik olarak kanıtlanmış 50 IgAN hastası, 25 sağlıklı (kontrol grubu) birey araştırmaya katılmıştır. ST6GALNAC2, C1GALT1 ve NEU1 genlerinin aminoasit kodlayan bölgelerinde, bu bölgelere yakın intron bölgelerinde ve promotör bölgelerinde nukleotit dizilimi yolu ile SNP taranması yapıldı. ST6GALNAC2 geninde IVS2+65insA, IVS2+12G>A, IVS3+39 T>C, Ala73Asp, Leu83Leu, IVS7-19T>C polimorfizimleri, C1GALT1 geninde ise c.-1625G>A, c.-1042G>C, c.-694C>T, c.-562C>T, 5'UTR-321 A>G, c.-517A>T, 5'UTR-1391ins21bp, 3'UTR+211G>A polimorfizimleri saptandı. Sonuçlar ST6GALNAC geninin intron bölgesinde saptanan IVS2+65insA polimorfizminin kontrol bireylere kıyaslamada IgAN hastalarında daha sık rastlandığını göstermiştir (p = 0.001 <0.05). IVS2 +12 G>A sadece IgAN hastalarında bulunmuştur. ST6GALNAC2. IVS7-19T>C (P=0,006; OR=0,2 0,09< IG95% <0,7) ve sadece kontrol bireyler arasında saptanan Ala73Asp (P=0.04) polimorfizimlerinin IgAN'den koruyucu rolleri vardır. NEU1 geninin IgAN hastalığıyla hiçbir ilişkisi saptanmadı.
IgA Nephropathy is a polygenic disorder. Increasing evidence has implicated that aberrant glycosylation of IgA1 molecules, including a2,6 sialic acid and galactose defects, are involved in the pathogenesis of IgAN. In the present study, we designed an association study to investigate polymorphisms of three important genes, ST6GALNAC2, C1GALT1 and NEU1 which are involved in the glycosylation of the IgA1 molecule, in the susceptibility to IgA Nephropathy. A total of 50 patients with histologically proven IgAN and 25 healthy controls were enrolled. Screening of SNPs in the coding, and promoter regions of the ST6GALNAC2, C1GALT1 and NEU1 genes was performed by sequencing. IVS2+65insA, IVS2+12G>A, IVS3+39 T>C, Ala73Asp, Leu83Leu, IVS7-19T>C in the ST6GALNAC2 gene and c.-1625G>A, c.-1042G>C, c.-694C>T, c.-562C>T, 5'UTR-321 A>G, c.-517A>T, 5'UTR-1391ins21bp, 3'UTR+211G>A in the C1GALT1 gene were detected. Our results demonstrated that the frequency of IVS2+65insA polymorphism in the intron region of ST6GALNAC2 was significantly higher in IgAN patients than that in controls (P=0.003<0.005; odds ratio [OR] 6,0; 95% confidence interval [CI], 1.78–20.258). IVS2+12G>A was found only in patients with IgAN. ST6GALNAC2. IVS7-19T>C (P=0,006; OR=0,2 0,09< IG95% <0,7) and Ala73Asp (P=0.04) polymorphism which was found only in controls have protective roles against IgAN disease. No association of NEU1 gene with IgAN was detected.
IgA Nephropathy is a polygenic disorder. Increasing evidence has implicated that aberrant glycosylation of IgA1 molecules, including a2,6 sialic acid and galactose defects, are involved in the pathogenesis of IgAN. In the present study, we designed an association study to investigate polymorphisms of three important genes, ST6GALNAC2, C1GALT1 and NEU1 which are involved in the glycosylation of the IgA1 molecule, in the susceptibility to IgA Nephropathy. A total of 50 patients with histologically proven IgAN and 25 healthy controls were enrolled. Screening of SNPs in the coding, and promoter regions of the ST6GALNAC2, C1GALT1 and NEU1 genes was performed by sequencing. IVS2+65insA, IVS2+12G>A, IVS3+39 T>C, Ala73Asp, Leu83Leu, IVS7-19T>C in the ST6GALNAC2 gene and c.-1625G>A, c.-1042G>C, c.-694C>T, c.-562C>T, 5'UTR-321 A>G, c.-517A>T, 5'UTR-1391ins21bp, 3'UTR+211G>A in the C1GALT1 gene were detected. Our results demonstrated that the frequency of IVS2+65insA polymorphism in the intron region of ST6GALNAC2 was significantly higher in IgAN patients than that in controls (P=0.003<0.005; odds ratio [OR] 6,0; 95% confidence interval [CI], 1.78–20.258). IVS2+12G>A was found only in patients with IgAN. ST6GALNAC2. IVS7-19T>C (P=0,006; OR=0,2 0,09< IG95% <0,7) and Ala73Asp (P=0.04) polymorphism which was found only in controls have protective roles against IgAN disease. No association of NEU1 gene with IgAN was detected.
Açıklama
Anahtar Kelimeler
IgAN, IgA1, C1GALT1, ST6GALNAC2, NEU1, Anormal Glikozilasyon, Sialik Asit, Galaktoz, IgAN Patogenezi, Aberrant Glycosylation, Sialic Acid, Galactose, Pathogenesis of IgAN
