Genetic Associations With Diabetes

The Big Diabetes Lie

Most Effective Diabetes Treatments

Get Instant Access

Recent advances in the genetic epidemiology of Type 1, Type 2 and MODY may soon make it possible to distinguish them based on genetic markers. Inheritance in European-origin MODY families usually follows that of an autosomal dominant pattern, with vertical transmission of disease from one generation to the next, and approximately 50% of siblings affected (28). Reports of non-Type 1 in other ethnic groups show vertical transmission in only a subset of such families (4). Work in Europeans and US whites has identified several associations of MODY with specific mutations (29); the HLA-DR and -DQ alleles linked to Type 1 diabetes are not found in MODY patients (27, 65). Indeed, some investigators suggest that patients with early-onset Type 2 diabetes can be distinguished from MODY patients on the basis of inheritance patterns (66).

There is widespread consensus that Type 2 diabetes, in contrast to MODY, is a genetically heterogeneous condition (45, 67). Familial aggregation is common, leading numerous investigators to search for relevant genes with limited success.

An array of polymorphisms have been linked to Type 2 diabetes and obesity in single families or ethnic groups, but no generalizable associations have yet emerged (65, 68, 69).

Among African-origin and Hispanic patients with 'typical' Type 1 diabetes, immunogenetic similarities to European-origin Type 1 diabetes patients have been demonstrated with a few notable exceptions. The strong association of Type 1 diabetes with alleles at the HLA-DR and -DQ loci has been confirmed among both African-origin patients and Latinos (40,70). In a case-control study from Colorado, Mexican American children with Type 1 diabetes were more likely than non-diabetic controls to have HLA-DR3, -DR4, and -DQ alleles which code for an amino acid other than aspartate at position 57 of the B1 subunit (non-Asp-57); similar findings were reported among non-Hispanic whites (71). The associated odds ratios were not significantly different by ethnicity, although fewer Mexican American patients carried DR3. Among blacks, similar strong associations with HLA-DR and -DQ alleles have been reported. Todd et al. (72) reported that the diabetes-associated DR9 haplo-type among Afro-Caribbean Type 1 diabetes patients in England carried a non-Asp codon at position 57 of DQB1, in contrast to DR9 among whites, which appears to be protective against IDDM and codes for Asp at dQb1-57 (73).

A positive family history is found in only 10-15% of Type 1 diabetes patients, while among Type 2 and MODY patients many relatives are affected. The frequency of diabetes among relatives of 9 atypical patients from Winter's clinic series was significantly higher than among relatives of 'typical' black (n = 5) and white (n = 11) Type 1 diabetes patients (74). Diabetes was ascertained in these relatives by patient or family report, and thus may also reflect differences in health care-seeking behaviors or other environmental risks.

A study of African American women reported that HLA-B41 and -DR2 were positively associated with risk of insulin-requiring gestational diabetes mellitus, and with risk of developing Type 2 diabetes in those with previous gestational diabetes (75). This report is interesting in light of the findings that older, ketosis-prone blacks with 'Flatbush' diabetes described by Banerji et al. showed a higher than expected frequency of the Type 1-associated HLA alleles (47). Evidently the strong association of HLA class II alleles with diabetes is not yet fully understood.

Was this article helpful?

0 0
Diabetes Sustenance

Diabetes Sustenance

Get All The Support And Guidance You Need To Be A Success At Dealing With Diabetes The Healthy Way. This Book Is One Of The Most Valuable Resources In The World When It Comes To Learning How Nutritional Supplements Can Control Sugar Levels.

Get My Free Ebook

Post a comment