Genome-wide scan for type 1 diabetic nephropathy in the Finnish population reveals suggestive linkage to a single locus on chromosome 3q
| Autor: | J. Tuomilehto, L. Albinsson, Karl Tryggvason, Janne Pitkäniemi, Anne-May Österholm, Bing He, Cinzia Sarti, T. Berg |
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| Rok vydání: | 2007 |
| Předmět: |
Adult
Male Adolescent Genetic Linkage Population 030209 endocrinology & metabolism Locus (genetics) Type 2 diabetes Biology Nephropathy Diabetic nephropathy 03 medical and health sciences 0302 clinical medicine Diabetes mellitus Chromosome regions medicine Humans Diabetic Nephropathies Genetic Predisposition to Disease Genetic Testing education Child Finland 030304 developmental biology Genetics 0303 health sciences Type 1 diabetes education.field_of_study diabetes Genome Human diabetic nephropathy genetic renal disease medicine.disease 3. Good health Diabetes Mellitus Type 1 Nephrology Female Chromosomes Human Pair 3 genome-wide scan |
| Zdroj: | Kidney International. 71(2):140-145 |
| ISSN: | 0085-2538 |
| DOI: | 10.1038/sj.ki.5001933 |
| Popis: | Diabetic nephropathy (DN) is the primary cause of morbidity and mortality in patients with type 1 as well as type 2 diabetes, and accounts for 40% of end-stage renal disease in the Western world. Familial clustering of DN suggests importance of genetic factors in the development of the disease. In the present study, we performed a two-stage genome-wide scan to search for chromosomal loci containing susceptibility genes for nephropathy in patients with type 1 diabetes. In total, 83 discordant sib pairs (DSPs), sibs concordant for type 1 diabetes but discordant for nephropathy, were collected from Finland, a homogeneous population with one of the highest incidences of type 1 diabetes. To map loci for DN, we applied DSP analysis to detect linkage. In the initial scan, 73 DSPs were typed using 900 markers with an average intermarker distance of approximately 4 cM. Multipoint DSP analysis identified five chromosome regions (3q, 4p, 9q, 16q, and 22p) with maximum logarithm of odds (LOD) score (MLS)or=1.0 (corresponding to a nominal P-valueor=0.015). In the second stage, additional 43 markers flanking these five loci were genotyped in all 83 DSPs. Using simulations, we determined the empirical threshold with LOD score of 1.76 and 3.12 for suggestive and significant linkage, respectively. No locus reached the genome-wide significance of 5%. However, one locus on 3q reached suggestive linkage with MLS of 2.67 (P=4.4 x 10(-4)). These results, together with data from others, suggest that the locus on 3q most likely has a susceptibility gene for DN. |
| Databáze: | OpenAIRE |
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