AIMS: Megsin is a mesangial cell-predominant gene which belongs to the serpin superfamily. The expression of megsin was upregulated and coincided with mesangial proliferation and extracellular matrix expansion in IgA nephropathy (IgAN). In the present study, we evaluated the influence of the C2093T and C2180T polymorphism within the 3' untranslated region (3'UTR) of megsin gene and its haplotypes on the development and progression of Korean IgAN patients. METHODS: Korean IgAN patients (n = 260) with a minimal follow-up of 4 years were recruited. Healthy subjects with normal renal function, normal urinalysis and normotension (n = 315) were included as controls. The polymorphisms were determined by the 5' nuclease allelic discrimination assay, and the haplotypes were constructed using the Phase program. RESULTS: The C2093T and C2180T genotype and allele frequencies were not different significantly between IgAN patients and controls. In C2093T polymorphism, patients with CC genotype showed a better renal survival than those with CT or TT genotypes by Kaplan-Meier analysis (p = 0.027). The megsin C2093T polymorphism remained an independent risk factor for progression (Cox regression model, HR for TT genotype: 3.52, 95% CI 1.69 - 7.34; HR for CT genotype: 2.15, 95% CI 1.30 - 3.57). In C2180T polymorphism, patients with TT genotype showed a better outcome than those with CC or CT genotypes (p = 0.025). The C2180T polymorphism was also an independent risk factor for progression (HR for CC genotype: 4.05, 95% CI 1.93 - 8.51; HR for CT genotype: 2.35, 95% CI 1.40 - 3.94). The two alleles showed linkage disequilibrium in phased haplotype. The patients with 2093T-2180C haplotype showed a poor renal survival compared to those with 2093C-2180T haplotype (p = 0.028). The haplotype remained an independent risk factor for progression (HR for 2093T-2180C haplotype: 2.01, 95% CI 1.44 - 2.81). CONCLUSIONS: Our results suggest that the 2093T-2180C haplotype at the 3'UTR of megsin gene is associated with rapid disease progression in Korean IgAN patients. This is the reverse of the results from the Chinese IgAN patients. Further studies are strongly needed to elucidate the reasons of disparity.
AIMS: Megsin is a mesangial cell-predominant gene which belongs to the serpin superfamily. The expression of megsin was upregulated and coincided with mesangial proliferation and extracellular matrix expansion in IgA nephropathy (IgAN). In the present study, we evaluated the influence of the C2093T and C2180T polymorphism within the 3' untranslated region (3'UTR) of megsin gene and its haplotypes on the development and progression of Korean IgANpatients. METHODS: Korean IgANpatients (n = 260) with a minimal follow-up of 4 years were recruited. Healthy subjects with normal renal function, normal urinalysis and normotension (n = 315) were included as controls. The polymorphisms were determined by the 5' nuclease allelic discrimination assay, and the haplotypes were constructed using the Phase program. RESULTS: The C2093T and C2180T genotype and allele frequencies were not different significantly between IgANpatients and controls. In C2093T polymorphism, patients with CC genotype showed a better renal survival than those with CT or TT genotypes by Kaplan-Meier analysis (p = 0.027). The megsinC2093T polymorphism remained an independent risk factor for progression (Cox regression model, HR for TT genotype: 3.52, 95% CI 1.69 - 7.34; HR for CT genotype: 2.15, 95% CI 1.30 - 3.57). In C2180T polymorphism, patients with TT genotype showed a better outcome than those with CC or CT genotypes (p = 0.025). The C2180T polymorphism was also an independent risk factor for progression (HR for CC genotype: 4.05, 95% CI 1.93 - 8.51; HR for CT genotype: 2.35, 95% CI 1.40 - 3.94). The two alleles showed linkage disequilibrium in phased haplotype. The patients with 2093T-2180C haplotype showed a poor renal survival compared to those with 2093C-2180T haplotype (p = 0.028). The haplotype remained an independent risk factor for progression (HR for 2093T-2180C haplotype: 2.01, 95% CI 1.44 - 2.81). CONCLUSIONS: Our results suggest that the 2093T-2180C haplotype at the 3'UTR of megsin gene is associated with rapid disease progression in Korean IgANpatients. This is the reverse of the results from the Chinese IgANpatients. Further studies are strongly needed to elucidate the reasons of disparity.
Authors: Caitrin W McDonough; Meredith A Bostrom; Lingyi Lu; Pamela J Hicks; Carl D Langefeld; Jasmin Divers; Josyf C Mychaleckyj; Barry I Freedman; Donald W Bowden Journal: Hum Genet Date: 2009-12 Impact factor: 4.132