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Title: The genetics of non-insulin dependent diabetes mellitus
Author: Alcolado, Juan Carlos
ISNI:       0000 0001 3410 2759
Awarding Body: University of Southampton
Current Institution: University of Southampton
Date of Award: 1991
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The genetics of non-insulin dependent diabetes mellitus (NIDDM) remain enigmatic. In order to investigate the molecular mechanisms, the family histories of a population of 1,326 patients were studied. A total of 391 (30%) had at least one affected first degree relative. Mothers were implicated in significantly more cases than fathers (126 diabetic mothers V. 48 fathers, p< 0.001). The implications of this apparent maternal transmission are discussed. At variance with a previous report, month of birth of affected subjects did not correlate with the development of either NIDDM or insulin dependent diabetes. Patients with at least one affected sibling and patients with indeterminate family history were recruited for DNA analysis. In order to test the hypothesis that genetic variants of the glucose transporter proteins may be responsible for the genetic susceptibility to NIDDM, both population association studies and affected member pedigree analyses were performed. In view of the recently reported linkage of a polymorphic mini-repeat marker at the adenosine deaminase locus and maturity onset diabetes of the young (MODY), a sib pair study was also performed at this site. The hypothesis that genetic variants at the collagen 1a IV locus may contribute genetic susceptibility to the development of diabetic retinopathy was tested with a population association study. Restriction fragment length polymorphisms (RFLPs) and a variable number tandem repeat (VNTR) were used as markers of DNA variation around candidate genes. Population association studies at the GLUT1 (expressed in erythrocytes and brain), GLUT4 (expressed in muscle and adipose cells) and collagen 1a IV (in the case of retinopaths) gene loci did not reveal any significant association between alleles of RFLPs and NIDDM or retinopathy. Sib-pair studies using a VNTR linked to the GLUT4 gene and a mini-repeat at the adenosine deaminase locus also yielded statistically insignificant results. Further studies conducted using a cDNA probe hybridising with the hepatocyte/β islet cell (GLUT2) gene region showed positive associations with alleles of Taq1, Bg11 and Kpn1 RFLPs in NIDDM subjects with affected siblings. These findings suggest that a gene variant of GLUT2 may be important in the transmission of the disease.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Genetics