Mitochondrial DNA sequence variation in Finnish patients with matrilineal diabetes mellitus
<p>Abstract</p> <p>Background</p> <p>The genetic background of type 2 diabetes is complex involving contribution by both nuclear and mitochondrial genes. There is an excess of maternal inheritance in patients with type 2 diabetes and, furthermore, diabetes is a common s...
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| Format: | Article |
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BMC
2012-07-01
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| Series: | BMC Research Notes |
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| Online Access: | http://www.biomedcentral.com/1756-0500/5/350 |
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| author | Soini Heidi K Moilanen Jukka S Finnila Saara Majamaa Kari |
| author_facet | Soini Heidi K Moilanen Jukka S Finnila Saara Majamaa Kari |
| author_sort | Soini Heidi K |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>The genetic background of type 2 diabetes is complex involving contribution by both nuclear and mitochondrial genes. There is an excess of maternal inheritance in patients with type 2 diabetes and, furthermore, diabetes is a common symptom in patients with mutations in mitochondrial DNA (mtDNA). Polymorphisms in mtDNA have been reported to act as risk factors in several complex diseases.</p> <p>Findings</p> <p>We examined the nucleotide variation in complete mtDNA sequences of 64 Finnish patients with matrilineal diabetes. We used conformation sensitive gel electrophoresis and sequencing to detect sequence variation. We analysed the pathogenic potential of nonsynonymous variants detected in the sequences and examined the role of the m.16189 T>C variant. Controls consisted of non-diabetic subjects ascertained in the same population. The frequency of mtDNA haplogroup V was 3-fold higher in patients with diabetes. Patients harboured many nonsynonymous mtDNA substitutions that were predicted to be possibly or probably damaging. Furthermore, a novel m.13762 T>G in <it>MTND5</it> leading to p.Ser476Ala and several rare mtDNA variants were found. Haplogroup H1b harbouring m.16189 T > C and m.3010 G > A was found to be more frequent in patients with diabetes than in controls.</p> <p>Conclusions</p> <p>Mildly deleterious nonsynonymous mtDNA variants and rare population-specific haplotypes constitute genetic risk factors for maternally inherited diabetes.</p> |
| first_indexed | 2024-12-19T02:24:54Z |
| format | Article |
| id | doaj.art-e5a06c5cc8d043aea2ccbbcdc37ce91d |
| institution | Directory Open Access Journal |
| issn | 1756-0500 |
| language | English |
| last_indexed | 2024-12-19T02:24:54Z |
| publishDate | 2012-07-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Research Notes |
| spelling | doaj.art-e5a06c5cc8d043aea2ccbbcdc37ce91d2022-12-21T20:39:59ZengBMCBMC Research Notes1756-05002012-07-015135010.1186/1756-0500-5-350Mitochondrial DNA sequence variation in Finnish patients with matrilineal diabetes mellitusSoini Heidi KMoilanen Jukka SFinnila SaaraMajamaa Kari<p>Abstract</p> <p>Background</p> <p>The genetic background of type 2 diabetes is complex involving contribution by both nuclear and mitochondrial genes. There is an excess of maternal inheritance in patients with type 2 diabetes and, furthermore, diabetes is a common symptom in patients with mutations in mitochondrial DNA (mtDNA). Polymorphisms in mtDNA have been reported to act as risk factors in several complex diseases.</p> <p>Findings</p> <p>We examined the nucleotide variation in complete mtDNA sequences of 64 Finnish patients with matrilineal diabetes. We used conformation sensitive gel electrophoresis and sequencing to detect sequence variation. We analysed the pathogenic potential of nonsynonymous variants detected in the sequences and examined the role of the m.16189 T>C variant. Controls consisted of non-diabetic subjects ascertained in the same population. The frequency of mtDNA haplogroup V was 3-fold higher in patients with diabetes. Patients harboured many nonsynonymous mtDNA substitutions that were predicted to be possibly or probably damaging. Furthermore, a novel m.13762 T>G in <it>MTND5</it> leading to p.Ser476Ala and several rare mtDNA variants were found. Haplogroup H1b harbouring m.16189 T > C and m.3010 G > A was found to be more frequent in patients with diabetes than in controls.</p> <p>Conclusions</p> <p>Mildly deleterious nonsynonymous mtDNA variants and rare population-specific haplotypes constitute genetic risk factors for maternally inherited diabetes.</p>http://www.biomedcentral.com/1756-0500/5/350Mitochondrial DNAdiabetesMitochondrial DNA haplogroupsm.16189 T>CMaternal inheritance |
| spellingShingle | Soini Heidi K Moilanen Jukka S Finnila Saara Majamaa Kari Mitochondrial DNA sequence variation in Finnish patients with matrilineal diabetes mellitus BMC Research Notes Mitochondrial DNA diabetes Mitochondrial DNA haplogroups m.16189 T>C Maternal inheritance |
| title | Mitochondrial DNA sequence variation in Finnish patients with matrilineal diabetes mellitus |
| title_full | Mitochondrial DNA sequence variation in Finnish patients with matrilineal diabetes mellitus |
| title_fullStr | Mitochondrial DNA sequence variation in Finnish patients with matrilineal diabetes mellitus |
| title_full_unstemmed | Mitochondrial DNA sequence variation in Finnish patients with matrilineal diabetes mellitus |
| title_short | Mitochondrial DNA sequence variation in Finnish patients with matrilineal diabetes mellitus |
| title_sort | mitochondrial dna sequence variation in finnish patients with matrilineal diabetes mellitus |
| topic | Mitochondrial DNA diabetes Mitochondrial DNA haplogroups m.16189 T>C Maternal inheritance |
| url | http://www.biomedcentral.com/1756-0500/5/350 |
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