Polymorphism in the Neuropeptide Y Y1/Y5 Receptor Gene Cluster is Associated with Proteinuria and Blood Pressure in Patients with IgA Nephropathy
A PstI RFLP has been described within the first intron of the human Neuropeptide Y Y1 receptor (NPYY1R) gene, which is the receptor subtype most likely to mediate renal and systemic vasoconstriction and is associated with antinatriuretic effects. Therefore, this RFLP and its clinical features in patients with IgA nephropathy was evaluated. A total of 105 patients with IgA nephropathy (49 males and 56 females) were genotyped, and the clinical findings in each genotype were compared. To evaluate the patients' long-termprognosis, only those who had a clinical course of over eight years duration were selected, and they were divided into a "poor-group" and a "fair-group", and compared their gene frequency in each group. The genotypes of the NPYY1R gene were determined by the PCR-RFLP method using the restriction enzyme PstI. The results suggested that RFLP is associated with blood pressure, as systolic blood pressure was significantly higher in the Yy and yy genotypes, compared to YY genotype [YY: 123.1 ± 18.2, Yy: 131.8 ± 16.9, yy: 132.0 ± 14.9 mmHg, (P<0.05; YY to Yy, p<0.05; YY to yy)] . With regard to proteinuria, the yy genotype tended to be severer than the YY genotype, although there was no significant correlation between Yy and YY [YY : 0.82 ± 0.69, Yy : 1.29 ± 1.46, yy : 1.87 ± 2.08 mg/24hr, (p<0.05 ; yy to YY)] . Most interestingly, however, was that 11 patients with massive proteinuria (>3g/24hr), had at least one y allele (YY; 0, Yy; 5 and yy; 6) suggesting a strong correlation between this y allele and proteinuria. These results suggest that this PstI RFLP of NPYY1R gene could be correlated with blood pressure and proteinuria, especially massive proteinuria in patients with IgA nephropathy.