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- Hemminki, Kari, et al.
(författare)
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Incidence of hereditary amyloidosis and autoinflammatory diseases in Sweden: endemic and imported diseases
- 2013
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Ingår i: BMC Medical Genetics. - : Springer Science and Business Media LLC. - 1471-2350. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Background: Amyloidoses are a heterogeneous group of progressive diseases caused by tissue deposition of misfolded proteins. According to the International Classification of Diseases, hereditary amyloidosis is divided into neuropathic and non-neuropathic forms. In Sweden, neuropathic heredofamilial amyloidosis has been identified as familial amyloidotic polyneuropathy (FAP), a fatal disease that is treated by liver transplantation. The non-neuropathic form includes familial autoinflammatory diseases. As no incidence data on these hereditary diseases are available and as even diagnostic data on non-neuropathic forms are lacking we determined the incidence of these diseases and characterized non-neuropathic conditions. Methods: Patients were identified using data from the Swedish Hospital Discharge Register and from the Outpatient Register for 2001 through 2008. All patients discharged with hereditary amyloidosis diagnoses were included and standardized incidence rates were calculated. Results: Non-neuropathic disease was diagnosed in 210 patients, with an incidence of 2.83 per million. FAP was diagnosed in 221 patients, with an incidence of 2.02 per million. Two northern provinces that are home to 5% of the Swedish population accounted for 77% of FAP cases; the incidence in one of them, West Bothnia, was 100 times that in the rest of Sweden. Approximately 98% of non-neuropathic disease patients were immigrants, most of whom were from the Eastern Mediterranean area. Young Syrian descendants had the highest incidence rate, which was over 500-fold higher than that in individuals with Swedish parents. Even the early onset of these conditions identified them as familial autoinflammatory diseases. Conclusions: FAP cases were highly concentrated in the two northernmost provinces. Non-neuropathic familial autoinflammatory diseases were of early-onset and immigrant origin most likely related to periodic fever syndromes. Paradoxically, FAP has remained endemic, in spite of population movements within the country, while familial autoinflammatory diseases, with an incidence exceeding that of FAP, were brought into the country as a result of immigration mainly from the Eastern Mediterranean area.
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| 2. |
- Huhn, Stefanie, et al.
(författare)
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Shared ancestral susceptibility to colorectal cancer and other nutrition related diseases
- 2012
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Ingår i: BMC Medical Genetics. - : Springer Science and Business Media LLC. - 1471-2350. ; 13:94
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Tidskriftsartikel (refereegranskat)abstract
- Background: The majority of non-syndromic colorectal cancers (CRCs) can be described as a complex disease. A two-stage case-control study on CRC susceptibility was conducted to assess the influence of the ancestral alleles in the polymorphisms previously associated with nutrition-related complex diseases. Methods: In stage I, 28 single nucleotide polymorphisms (SNPs) were genotyped in a hospital-based Czech population (1025 CRC cases, 787 controls) using an allele-specific PCR-based genotyping system (KASPar (R)). In stage II, replication was carried out for the five SNPs with the lowest p values. The replication set consisted of 1798 CRC cases and 1810 controls from a population-based German study (DACHS). Odds ratios (ORs) and 95% confidence intervals (CIs) for associations between genotypes and CRC risk were estimated using logistic regression. To identify signatures of selection, Fay-Wu's H and Integrated Haplotype Score (iHS) were estimated. Results: In the Czech population, carriers of the ancestral alleles of AGT rs699 and CYP3A7 rs10211 showed an increased risk of CRC (OR 1.26 and 1.38, respectively; two-sided p <= 0.05), whereas carriers of the ancestral allele of ENPP1 rs1044498 had a decreased risk (OR 0.79; p <= 0.05). For rs1044498, the strongest association was detected in the Czech male subpopulation (OR 0.61; p=0.0015). The associations were not replicated in the German population. Signatures of selection were found for all three analyzed genes. Conclusions: Our study showed evidence of association for the ancestral alleles of polymorphisms in AGT and CYP3A7 and for the derived allele of a polymorphism in ENPP1 with an increased risk of CRC in Czechs, but not in Germans. The ancestral alleles of these SNPs have previously been associated with nutrition-related diseases hypertension (AGT and CYP3A7) and insulin resistance (ENPP1). Future studies may shed light on the complex genetic and environmental interactions between different types of nutrition-related diseases.
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| 3. |
- Lascorz, Jesus, et al.
(författare)
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Polymorphisms in the mitochondrial oxidative phosphorylation chain genes as prognostic markers for colorectal cancer
- 2012
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Ingår i: BMC Medical Genetics. - : Springer Science and Business Media LLC. - 1471-2350. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background: Currently, the TNM classification of malignant tumours based on clinicopathological staging remains the standard for colorectal cancer (CRC) prognostication. Recently, we identified the mitochondrial oxidative phosphorylation chain as a consistently overrepresented category in the published gene expression profiling (GEP) studies on CRC prognosis. Methods: We evaluated associations of putative regulatory single nucleotide polymorphisms (SNPs) in genes from the oxidative phosphorylation chain with survival and disease prognosis in 613 CRC patients from Northern Germany (PopGen cohort). Results: Two SNPs in the 3' untranslated region of UQCRB (complex III), rs7836698 and rs10504961, were associated with overall survival (HR = 0.52, 95% CI 0.32-0.85 and HR = 0.64, 95% CI 0.42-0.99, for TT carriers). These associations were restricted to the group of patients with cancer located in the colon (HR = 0.42, 95% CI 0.22-0.82 and HR = 0.46, 95% CI 0.25-0.83). Multivariate analysis indicated that both markers might act as independent prognostic markers. Additionally, the TT carriers were similar to 2 times more likely to develop tumours in the colon than in the rectum. Two SNPs in COX6B1 (complex IV) were associated with lymph node metastasis in a dominant model (rs6510502, OR = 1.75, 95% CI 1.20-2.57; rs10420252, OR = 1.68, 95% CI 1.11-2.53); rs6510502 was associated also with distant metastasis (OR = 1.67, 95% CI 1.09-2.56 in a dominant model). Conclusions: This is the first report suggesting that markers in genes from the mitochondrial oxidative chain might be prognostic factors for CRC. Additional studies replicating the presented findings are needed.
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