Genes within and flanking the major histocompatibility region are risk factors for diabetes, insulin resistance, hypertension, and microalbuminuria in African-American women

Acton, Ronald T.; Bell, David S.H.; Collins, Jenny; Giger, Joyce Newman; Go, Rodney C.P.; Harrison, Renée A.; McDonald, Rosemary; Rivers, Charles A.; Roseman, Jeffrey M.; Taylor, Herman A.; Vanichanan, Chotip

doi:10.1016/s0041-1345(97)01079-8

Cited by 13 publications

(5 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is uncertain whether the risk burden could be in part related to HLA. Some, but not all, previous epidemiologic studies suggested increase in cardiovascular risk in individuals with certain HLA genotypes (3,4,13). In our cohort, incipient retinopathy was detected in only few patients, without any clear difference between the DQ2/8 groups.…”

Section: Discussioncontrasting

confidence: 59%

Cutaneous Microvascular Dysfunction Is Associated With Human Leukocyte Antigen-DQ in Youths With Type 1 Diabetes

et al. 2008

View full text Add to dashboard Cite

Functional disturbances in microcirculation in juvenile type 1 diabetes (T1D) are believed to underlie, in part, the later occurrence of cardiovascular complications. Some epidemiologic studies suggested greater risk of microvascular complications in those with T1D-risk genotypes of human leukocyte antigen (HLA). We investigated whether HLA-DQ2/8, which is linked to highest T1D morbidity, influences microvascular function in young diabetic patients. Cutaneous microvascular endothelium-dependent and independent reactivity and HLA genotypes were assessed in young patients (age: 9 -21 y) with T1D (duration: 2-20 y). HLA-DQ2/8 was identified in 29 of 75 patients. The DQ2/8 and non-DQ2/8 groups were similar in age, body mass index, diabetes duration, glycosylated hemoglobin, and C-reactive protein (CRP). Compared with the non-DQ2/8 group, the DQ2/8 group showed decreased endotheliumdependent responses (p ϭ 0.03 after adjustment for age, diabetes duration, glycosylated hemoglobin, and CRP) and elevated soluble intercellular adhesion molecule-1 (p ϭ 0.05). In these but not in non-DQ2/8 patients, CRP correlated with both systolic (r ϭ 0.76; p Ͻ 0.001) and diastolic (r ϭ 0.50; p ϭ 0.01) blood pressure. HLA-DQ2/8 is associated with endothelial microvascular dysfunction in young patients with T1D, and future studies are needed to provide mechanistic insights. The findings could explain in part the previously reported epidemiologic link between T1D-risk HLA and microvascular complications. A broad spectrum of cardiovascular risk factors including type 1 diabetes (T1D) has been linked to functional disturbances in microcirculation. The generalized microvascular dysfunction in T1D is an important mechanism in the development of microvascular diabetes complications in, for instance, eyes, kidneys, or myocardium (1). Although the precise pathophysiology of diabetes microvasculopathy remains elusive, it seems that both extrinsic (e.g., infection, socioeconomic status) and intrinsic (race, ethnicity, metabolic control) factors contribute to it, in part, through progressive injury to microvascular endothelial cells (2).Some, but not all, previous epidemiologic works suggested a possible link between the human leukocyte antigen (HLA) system and clinical manifestations of microvasculopathy in both diabetic and nondiabetic patients (3,4). Expression of diabetes-risk HLA class II molecules on islet endothelial cells could be a central vascular event in the pathogenesis of T1D (5). Previous studies showing the ability of endothelial cells in other vascular beds to express HLA class II support the assumption that HLA may be present in the entire vascular system (6,7). Whether diabetes-risk HLA is associated with systemic microvascular endothelial dysfunction has not yet been studied.Herein, we investigated the relationship between the HLA-DQ2/8 genotype, which confers the highest risk for T1D (8) and endothelial function of cutaneous microcirculation in young patients with T1D. METHODSSeventy-five children and adolescents (45 ...

show abstract

Section: Discussioncontrasting

confidence: 59%

Cutaneous Microvascular Dysfunction Is Associated With Human Leukocyte Antigen-DQ in Youths With Type 1 Diabetes

et al. 2008

View full text Add to dashboard Cite

show abstract

“…At least one study reported that genes flanking the major histocompatibility complex are associated with diabetes mellitus, insulin resistance, hypertension and moderately increased albuminuria in black women with a history of GDM. 55 Black women have been shown to develop hypertension, a risk factor for CKD, more often and more rapidly following a GDM pregnancy compared to white women. 56 In our cohort, black women were more likely than white women to develop hypertension prior to onset of albuminuria, however the presence of hypertension did not seem to account for the association between incident albuminuria and GDM seen among black women.…”

Section: Discussionmentioning

confidence: 99%

Association Between Gestational Diabetes and Incident Maternal CKD: The Coronary Artery Risk Development in Young Adults (CARDIA) Study

Dehmer

Phadnis

Gunderson

et al. 2018

American Journal of Kidney Diseases

View full text Add to dashboard Cite

show abstract

“…After screening the full-text of the papers, we excluded 34 from the study because they were functional studies or presented duplicate data sets or they did not supply sufficient data about HLA polymorphisms. In our analysis, we finally employed a total of 16 studies 11 13 15 16 17 18 19 21 22 23 24 25 26 27 28 29 and their characteristic features are summarized in Table 1 . The flow of our study is illustrated in Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Some HLA class II variants, such as DQB1*02 11 , DQB1*0201 19 , DQB1*0203 16 , DQB1*0301 21 , DQB1*0402 16 , DRB1*01 13 , DRB1*02 13 , DRB1*0301 18 , DRB1*1302 18 and DR1 26 have been implicated in GDM development in association studies. However, our meta-analysis result could only confirm the associations for DQB1*02 and DRB1*1302 with GDM.…”

Section: Discussionmentioning

confidence: 99%

“…Previous association studies have suggested a role for HLA class II variants in the pathogenesis of GDM. For HLA-DQ alleles, DQB1*02 was reported to be positively associated with GDM in African-American 13 and Swedish 11 populations, while DQB1*0602 14 15 and DQB1*0402 16 were negatively related with GDM in Swedish and Chinese populations, respectively. For HLA-DR variants, DR5 17 has been found to be negatively associated with GDM in Italian patients, while DRB1*0301 18 and DRB1*1302 19 were positively linked with GDM in Chinese patients.…”

mentioning

confidence: 98%

See 1 more Smart Citation

The relationships between HLA class II alleles and antigens with gestational diabetes mellitus: A meta-analysis

Guo

Jin

Lee

et al. 2016

Sci Rep

View full text Add to dashboard Cite

Gestational diabetes mellitus (GDM) is defined as glucose intolerance with onset or first recognition during pregnancy. It is associated with an increased risk of pregnancy complications. Susceptibility to GDM is partly determined by genetics and linked with type 1 diabetes-associated high risk HLA class II genes. However, the evidence for this relationship is still highly controversial. In this study, we assessed the relationship between HLA class II variants and GDM. We performed meta-analysis on all of literatures available in PubMed, Embase, Web of Science and China National Knowledge Infrastructure databases. The odds ratio and 95% confidence interval of each variant were estimated. All statistical analyses were conducted using the Comprehensive Meta Analysis 2.2.064 software. At the allelic analysis, DQB1*02, DQB1*0203, DQB1*0402, DQB1*0602, DRB1*03, DRB1*0301 and DRB1*1302 reached a nominal level of significance, and only DQB1*02, DQB1*0602 and DRB1*1302 were statistically significant after Bonferroni correction. At the serological analysis, none of DQ2, DQ6, DR13 and DR17 was statistically significant following Bonferroni correction although they reached a nominal level of significance. In sum, our meta-analysis demonstrated that there were the associations between HLA class II variants and GDM but more studies are required to elucidate how these variants contribute to GDM susceptibility.Gestational diabetes mellitus (GDM) is defined as glucose intolerance with onset during pregnancy 1 . The manifestation of GDM is reportedly influenced by age 2 , ethnicity 3 , BMI 4 , and family history of GDM of the pregnant woman 5 . Despite all this information, the pathogenesis of GDM still remains obscure. Since GDM is regarded as a risk factor for developing type 2 diabetes 6 , many investigators have mainly focused on the linkage between GDM and type 2 diabetes. However, Lapolla et al. 7 reported that presentation of pancreatic islet autoantibodies during GDM is predictive for type 1 diabetes development. A number of studies have demonstrated that the circulating immune markers of type 1 diabetes (such as anti-islet cell antibodies and anti-GAD antibodies) are present in the blood of pregnant women with GDM [8][9][10][11] . There is no doubt that we could understand the pathology underlying GDM better, if more genetic risk variants that are shared by type 1 diabetes and GDM were identified. The major type 1 diabetes susceptibility variants are HLA class II genes located on chromosome 6p21, which account for up to 30-50% of the heritability of type

show abstract

Genes within and flanking the major histocompatibility region are risk factors for diabetes, insulin resistance, hypertension, and microalbuminuria in African-American women

Cited by 13 publications

References 17 publications

Cutaneous Microvascular Dysfunction Is Associated With Human Leukocyte Antigen-DQ in Youths With Type 1 Diabetes

Cutaneous Microvascular Dysfunction Is Associated With Human Leukocyte Antigen-DQ in Youths With Type 1 Diabetes

Association Between Gestational Diabetes and Incident Maternal CKD: The Coronary Artery Risk Development in Young Adults (CARDIA) Study

The relationships between HLA class II alleles and antigens with gestational diabetes mellitus: A meta-analysis

Contact Info

Product

Resources

About