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The interleukin-1 gene cluster: A ca...
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Bensen, Jeannette Taylor.
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The interleukin-1 gene cluster: A candidate for end-stage renal disease.
紀錄類型:
書目-語言資料,印刷品 : Monograph/item
正題名/作者:
The interleukin-1 gene cluster: A candidate for end-stage renal disease./
作者:
Bensen, Jeannette Taylor.
面頁冊數:
212 p.
附註:
Adviser: Donald W. Bowden.
Contained By:
Dissertation Abstracts International63-02B.
標題:
Biology, Genetics. -
電子資源:
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3043095
ISBN:
0493566406
The interleukin-1 gene cluster: A candidate for end-stage renal disease.
Bensen, Jeannette Taylor.
The interleukin-1 gene cluster: A candidate for end-stage renal disease.
- 212 p.
Adviser: Donald W. Bowden.
Thesis (Ph.D.)--Wake Forest University, The Bowman Gray School of Medicine, 2002.
The results of these studies are consistent with multiple genes in the ILA gene cluster being associated with ESRD susceptibility.
ISBN: 0493566406Subjects--Topical Terms:
1017730
Biology, Genetics.
The interleukin-1 gene cluster: A candidate for end-stage renal disease.
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The results of these studies are consistent with multiple genes in the ILA gene cluster being associated with ESRD susceptibility.
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End Stage Renal Disease (ESRD) is a major public health problem in the United States. A hallmark of ESRD pathogenesis is inflammation, characterized by glomerular basement membrane thickening and mesangial expansion. Recent studies have suggested an association between alleles in the IL1RN gene and diabetic nephropathy. The IL1RN gene is one of multiple inflammation-associated genes in the IL1 gene cluster on human chromosome 2q13–14.1. Consequently, a detailed molecular genetic analysis of this genomic region was carried out to identify genes that contribute to ESRD susceptibility. A dense SNP map was constructed covering the 360 kilobases (kb) of the IL1 gene cluster. Ninety-six polymorphisms were identified in IL1A (14 SNPs, 1 insertion/deletion), IL1B (5 SNPs, 1 intergenic tetranucleotide repeat), IL1F10 (6 SNPs) and IL1RN (1 VNTR, 3 single base I/Ds and 65 SNPs). The 96 polymorphisms were genotyped in 443 case-control subjects; 95 Caucasian controls, 75 Caucasians with type 2 diabetes mellitus (T2DM)-associated ESRD, 86 African American controls, 92 African Americans with T2DM-associated ESRD and 95 African Americans with non-T2DM-associated ESRD. Genotype data were used to identify disease-associated markers or haplotypes as well as to describe linkage disequilibrium (LD) across this region in both ethnic groups. In all, 11 single markers and five, three-marker disease associated haplotypes were identified (P < 0.05), with the majority observed in African American Non-T2DM/ESRD. The two most significant disease-associated markers were located in IL1A (P = 0.0024 and P = 0.0015). LD was not strictly correlated with distance, however a trend of decreasing LD with distances greater than 50 kb was observed, with higher LD in Caucasians.
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In addition to this comprehensive genomic analysis, a 450 bp region of sequence similar to IL1RN was identified. This hypothetical gene fragment was expressed in THP-1 cell mRNA, and a number of human tissues. The full-length cDNA sequence of the gene, designated IL1F10, was obtained using rapid amplification of cDNA ends (RACE). IL1F10 mapped between IL1B and IL1RN. Six IL1F10 exonic allelic variants were identified using SSCP. These additional SNPs were included in the IL1 gene cluster SNP map.
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Another detailed analysis of the IL1A gene lead to the experimental identification of 2 SNPs flanking a 4 by I/D in the IL1A 3<super>′</super>UTR. An evaluation of the I/D polymorphism by SSCP in case-control subjects showed association among African Americans with non-T2DM ESRD. Subsequent studies revealed a decrease in IL1 α protein levels with increasing copies of the insertion allele in both Caucasian and African Americans.
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School code: 0249.
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