TY - JOUR
T1 - Meprin β metalloprotease gene polymorphisms associated with diabetic nephropathy in the Pima Indians
AU - Red Eagle, Alexander R.
AU - Hanson, Robert L.
AU - Jiang, Weiping
AU - Han, Xiaoli
AU - Matters, Gail L.
AU - Imperatore, Giuseppina
AU - Knowler, William C.
AU - Bond, Judith S.
N1 - Funding Information:
Acknowledgements We thank the members of the Gila River Indian Community who participated in this study. We also thank Dr. Joseph Giacalone in Dr. Uta Francke’s laboratory at Stanford University for screening the CEPH Mega YAC library with the provided primer sequences. We thank Drs. Ellen Brundage and Craig Chinault from the Cloning Core of the Human Genome Center at Baylor College of Medicine for providing clones YAC898C4 and 928G1. This work was supported by National Institutes of Health Grants DK 19691 and 54625, and by the intramural research program of the NIDDK.
PY - 2005/11
Y1 - 2005/11
N2 - There is evidence that susceptibility to diabetic nephropathy has a significant genetic component. This investigation tested the hypothesis that variations in the structural or regulatory regions of the MEP1B gene are related to susceptibility to diabetic nephropathy in the Pima Indian population. The structure of the human MEP1B gene on chromosome 18 was determined by polymerase chain reaction (PCR) amplification. Samples from 154 diabetic individuals were analyzed for polymorphisms. These individuals belonged to 65 sibships with at least one sibling pair discordant for diabetic nephropathy. Approximately half of the individuals had diabetic nephropathy. Of the 154 samples, there were 91 discordant sibling pairs. Sequencing revealed 19 single nucleotide polymorphisms (SNPs) in the MEP1B gene. SNPs 1-5 were in the 5′ region upstream of the start site for transcription; SNPs 6, 7, 9, 11-15, 17, and 19 were within introns; SNPs 8, 10, 16, and 18 were in exons 4, 9, 12, and 14. SNP 18 was the only one that results in an amino acid change (proline to leucine in the cytoplasmic tail). No overall associations were found for individual SNPs. Within-family association tests found significant results for SNPs 1, 3, 4, 5, 6, 9, 11, 18, and 19 such that the more common allele was more frequently observed in those with nephropathy than in their unaffected siblings. The present study demonstrates significant within-family association for SNPs in MEP1B gene with diabetic nephropathy. These results could be explained by functional effects of one or more of these SNPs or by linkage disequilibrium with a nearby functional locus.
AB - There is evidence that susceptibility to diabetic nephropathy has a significant genetic component. This investigation tested the hypothesis that variations in the structural or regulatory regions of the MEP1B gene are related to susceptibility to diabetic nephropathy in the Pima Indian population. The structure of the human MEP1B gene on chromosome 18 was determined by polymerase chain reaction (PCR) amplification. Samples from 154 diabetic individuals were analyzed for polymorphisms. These individuals belonged to 65 sibships with at least one sibling pair discordant for diabetic nephropathy. Approximately half of the individuals had diabetic nephropathy. Of the 154 samples, there were 91 discordant sibling pairs. Sequencing revealed 19 single nucleotide polymorphisms (SNPs) in the MEP1B gene. SNPs 1-5 were in the 5′ region upstream of the start site for transcription; SNPs 6, 7, 9, 11-15, 17, and 19 were within introns; SNPs 8, 10, 16, and 18 were in exons 4, 9, 12, and 14. SNP 18 was the only one that results in an amino acid change (proline to leucine in the cytoplasmic tail). No overall associations were found for individual SNPs. Within-family association tests found significant results for SNPs 1, 3, 4, 5, 6, 9, 11, 18, and 19 such that the more common allele was more frequently observed in those with nephropathy than in their unaffected siblings. The present study demonstrates significant within-family association for SNPs in MEP1B gene with diabetic nephropathy. These results could be explained by functional effects of one or more of these SNPs or by linkage disequilibrium with a nearby functional locus.
UR - https://www.scopus.com/pages/publications/24944507963
UR - https://www.scopus.com/inward/citedby.url?scp=24944507963&partnerID=8YFLogxK
U2 - 10.1007/s00439-005-0019-7
DO - 10.1007/s00439-005-0019-7
M3 - Article
C2 - 16133184
AN - SCOPUS:24944507963
SN - 0340-6717
VL - 118
SP - 12
EP - 22
JO - Human genetics
JF - Human genetics
IS - 1
ER -
