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- Astuti, D, et al.
(författare)
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Gene mutations in the succinate dehydrogenase subunit SDHB cause susceptibility to familial pheochromocytoma and to familial paraganglioma.
- 2001
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 69:1, s. 49-54
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Tidskriftsartikel (refereegranskat)abstract
- The pheochromocytomas are an important cause of secondary hypertension. Although pheochromocytoma susceptibility may be associated with germline mutations in the tumor-suppressor genes VHL and NF1 and in the proto-oncogene RET, the genetic basis for most cases of nonsyndromic familial pheochromocytoma is unknown. Recently, pheochromocytoma susceptibility has been associated with germline SDHD mutations. Germline SDHD mutations were originally described in hereditary paraganglioma, a dominantly inherited disorder characterized by vascular tumors in the head and the neck, most frequently at the carotid bifurcation. The gene products of two components of succinate dehydrogenase, SDHC and SDHD, anchor the gene products of two other components, SDHA and SDHB, which form the catalytic core, to the inner-mitochondrial membrane. Although mutations in SDHC and in SDHD may cause hereditary paraganglioma, germline SDHA mutations are associated with juvenile encephalopathy, and the phenotypic consequences of SDHB mutations have not been defined. To investigate the genetic causes of pheochromocytoma, we analyzed SDHB and SDHC, in familial and in sporadic cases. Inactivating SDHB mutations were detected in two of the five kindreds with familial pheochromocytoma, two of the three kindreds with pheochromocytoma and paraganglioma susceptibility, and 1 of the 24 cases of sporadic pheochromocytoma. These findings extend the link between mitochondrial dysfunction and tumorigenesis and suggest that germline SDHB mutations are an important cause of pheochromocytoma susceptibility.
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- Astuti, D, et al.
(författare)
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SLIT2 promoter methylation analysis in neuroblastoma, Wilms' tumour and renal cell carcinoma.
- 2004
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Ingår i: British journal of cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 90:2, s. 515-21
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Tidskriftsartikel (refereegranskat)abstract
- The 3p21.3 RASSF1A tumour suppressor gene (TSG) provides a paradigm for TSGs inactivated by promoter methylation rather than somatic mutations. Recently, we identified frequent promoter methylation without somatic mutations of SLIT2 in lung and breast cancers, suggesting similarities between SLIT2 and RASSF1A TSGs. Epigenetic inactivation of RASSF1A was first described in lung and breast cancers and subsequently in a wide range of human cancers including neuroblastoma, Wilms' tumour and renal cell carcinoma (RCC). These findings prompted us to investigate SLIT2 methylation in these three human cancers. We analysed 49 neuroblastomas (NBs), 37 Wilms' tumours and 48 RCC, and detected SLIT2 promoter methylation in 29% of NB, 38% of Wilms' tumours and 25% of RCC. Previously, we had demonstrated frequent RASSF1A methylation in the same tumour series and frequent CASP8 methylation in the NB and Wilms' tumour samples. However, there was no significant association between SLIT2 promoter methylation and RASSF1A or CASP8 methylation in NB and RCC. In Wilms' tumour, there was a trend for a negative association between RASSF1A and SLIT2 methylation, although this did not reach statistical significance. No associations were detected between SLIT2 promoter methylation and specific clinicopathological features in the tumours analysed. These findings implicate SLIT2 promoter methylation in the pathogenesis of both paediatric and adult cancers and suggest that further investigations of SLIT2 in other tumour types should be pursued. However, epigenetic inactivation of SLIT2 is less frequent than RASSF1A in the tumour types analysed.
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- Sayeed, M Abu, et al.
(författare)
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Diabetes and impaired fasting glycemia in a rural population of Bangladesh
- 2003
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 26:4, s. 1034-1039
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To determine the prevalence of type 2 diabetes and impaired fasting glycemia (IFG) in a rural population of Bangladesh. RESEARCH DESIGN AND METHODS: A cluster sampling of 4,923 subjects >/=20 years old in a rural community were investigated. Fasting plasma glucose, blood pressure, height, weight, and girth of waist and hip were measured. BMI and waist-to-hip ratio (WHR) were calculated. Total cholesterol, triglycerides, and HDL cholesterol were also estimated. We used the 1997 American Diabetes Association diagnostic criteria. RESULTS: The crude prevalence of type 2 diabetes was 4.3% and IFG was 12.4%. The age-standardized prevalence of type 2 diabetes (95% CI) was 3.8% (3.12-4.49) and IFG was 13.0% (11.76-14.16). The subjects with higher family income had significantly higher prevalence of type 2 diabetes (5.9 vs. 3.5%, P < 0.001) and IFG (15.6 vs. 10.8%, P < 0.001) than those with lower income. Employing logistic regression in different models, we found that wealthy class, family history of diabetes, reduced physical exercise, and increased age, BMI, and WHR were the important predictors of diabetes. Total cholesterol, triglycerides, and HDL cholesterol showed no association with diabetes and IFG. CONCLUSIONS: The prevalence of diabetes and IFG in the rural population was found to be on the increase compared with the previous reports of Bangladesh and other Asian studies. Older age, higher obesity, higher income, family history of diabetes, and reduced physical activity were proved significant risk factors for diabetes and IFG, whereas plasma lipids showed no association with diabetes and IFG. Further study may address whether diabetes is causally associated with insulin deficiency or insulin resistance.
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