ABSTRACT
BACKGROUND: The insertion/deletion (I/D) polymorphism of angiotensin converting enzyme (ACE) gene has been associated with progression of renal diseases. AIMS: We investigated its role in the rate of progression of focal segmental glomerulosclerosis (FSGS). METHODS: Forty-seven patients with end-stage renal disease (ESRD) due to FSGS were evaluated. RESULTS: The distribution of ACE genotype was II-25.5%, ID-55.5%, and DD-19%, as compared to 40 controls with genotype of 7.5%, 60%, and 32.5%, respectively (p= NS). In African Americans (AA) the gene frequencies among patients and controls were I-43%, D-57% vs I-36%, D-64%, respectively. This was different than the gene frequencies in White/Hispanic (W/H) patients I-61.5%, D-38.5% vs I-38.6%, D-61.4%, in controls (P < 0.05). In 22 patients with rapid progression (RP) of FSGS to ESRD the genotype distribution was II-18%, ID -64%, and DD-18%. In 25 patients with FSGS who progressed slowly (SP) the genotype was similar (II-32%, ID-48% and DD-20%, P >0.05). With respect to rate of progression, D allele frequency was similar in AA patients (RP 64% vs SP 50%) and W/H patients (RP 36% vs SP 40%). CONCLUSION: Our study reveals no association between the I/D polymorphism of the ACE gene and the presence of and rapidity progression of FSGS.
Subject(s)
Glomerulosclerosis, Focal Segmental/genetics , Peptidyl-Dipeptidase A/genetics , Polymorphism, Genetic , Adolescent , Adult , Alleles , Black People/genetics , Child , Disease Progression , Female , Genotype , Humans , Male , Middle Aged , White People/geneticsABSTRACT
The PKHD1 (polycystic kidney and hepatic disease 1) gene responsible for autosomal recessive polycystic kidney disease has been mapped to 6p21.1-p12 to an approximately 1-cM interval flanked by the markers D6S1714/D6S243 and D6S1024. We have developed a sequence-ready BAC/PAC-based contig map of this region as the next step for the positional cloning of PKHD1. This contig comprising 52 clones spanning approximately 1 Mb was established by content mapping of 44 BAC/PAC-end-derived STSs, 3 known genetic markers, 5 YAC-end-derived STSs, 3 random STSs, 1 previously mapped gene, and 1 EST. The average depth per marker is 6.3 clones, and the average STS density is 20 kb. The genomic clone overlaps were confirmed by restriction fragment fingerprint analysis. A high-resolution BAC/PAC-based contig map is essential to the ultimate goal of identifying the PKHD1 gene.
Subject(s)
Chromosomes, Human, Pair 6/genetics , DNA/genetics , Polycystic Kidney, Autosomal Recessive/genetics , Contig Mapping , DNA/analysis , DNA Fingerprinting , Electrophoresis, Gel, Pulsed-Field , Humans , Sequence Tagged SitesABSTRACT
Autosomal recessive polycystic kidney disease is one of the most common hereditary renal cystic diseases in children. Genetic studies have recently assigned the only known locus for this disorder, PKHD1, to chromosome 6p21-p12. We have generated a YAC contig that spans approximately 5 cM of this region, defined by the markers D6S1253-D6S295, and have mapped 43 sequence-tagged sites (STS) within this interval. This set includes 20 novel STSs, which define 12 unique positions in the region, and three ESTs. A minimal set of two YACs spans the segment D6S465-D6S466, which contains PKHD1, and estimates of their sizes based on information in public databases suggest that the size of the critical region is < 3.1 Mb. Twenty-eight STSs map to this interval, giving an average STS density of < 1/150 kb. These resources will be useful for establishing a complete transcription map of the PKHD1 region.
