ABSTRACT
Tumor necrosis factor alpha (TNF-alpha) -308 G/A and lymphotoxin alpha (LTalpha) +249 A/G single-nucleotide polymorphisms were investigated in 228 type 1 diabetes mellitus (T1DM) patients and 240 controls. Only LTalpha +249G allele and +249G/+249G genotype frequencies were higher among patients, and no linkage disequilibrium was found between TNF-alpha/LTalpha alleles and susceptible/protective DRB1-DQB1 haplotypes. TNF-alpha/LTalpha T1DM-susceptible (-308G/+249G) and protective (-308G/+249A) haplotypes were identified.
Subject(s)
Diabetes Mellitus, Type 1/genetics , Genetic Predisposition to Disease , HLA-DQ Antigens/genetics , Linkage Disequilibrium , Lymphotoxin-alpha/genetics , Tumor Necrosis Factor-alpha/genetics , Adolescent , Adult , Bahrain , Child , Child, Preschool , Female , Gene Frequency , Genotype , HLA-DQ beta-Chains , Haplotypes , Humans , Male , Polymorphism, GeneticABSTRACT
CONTEXT: Human leukocyte antigen (HLA) class II genes contribute to the genetic susceptibility of type 1 diabetes (T1D), and both susceptible and protective alleles were implicated with its pathogenesis, which varies among various ethnic/racial groups. OBJECTIVE: This study investigated the heterogeneity in HLA class II haplotypes distribution among Bahraini and Lebanese T1D patients. DESIGN: This was a cross-sectional retrospective study. SETTING: The study was conducted at primary care private and public health centers. PATIENTS AND OTHER PARTICIPANTS: Subjects comprised 126 T1D patients and 126 healthy controls from Bahrain and 78 Lebanese T1D patients and 111 control subjects. INTERVENTION(S): There were no interventions. RESULTS: Although Lebanese and Bahraini patients share DRB1*030101, DQB1*0201 as susceptible and DRB1*100101 and DQB1*030101 as protective alleles, DRB1*040101 was an additional susceptible allele in Bahraini patients, and DRB1*130701 and DQB1*050101 were additional susceptible and protective alleles in Lebanese, respectively. DRB1*030101-DQB1*0201 was susceptible, whereas DRB1*070101-DQB1*0201 and DRB1*110101-DQB1*030101 were protective haplotypes in Bahraini and Lebanese. DRB1*040101-DQB1*0302 and DRB1*040101-DQB1*050101 displayed different associations: they were protective in Lebanese but susceptible or neutral among Bahrainis. Whereas the frequency of homozygous DRB1*03011-DQB1*0201 was higher in Bahraini and to a lesser extent Lebanese patients, homozygous DRB1*110101-DQB1*030101 was significantly more frequent in Lebanese but not Bahraini controls, whereas DRB1*030101-DQB1*0201/DRB1*040101-DQB1*0201 was the major genotype among Bahraini patients but not Lebanese subjects in whom it was present at very low frequencies. CONCLUSION: In view of these differences between Bahraini and Lebanese, this demonstrates that the contribution of HLA class II to the genetic susceptibility to T1D must be evaluated with regard to specific HLA haplotypes and also ethnic origin and racial background.
Subject(s)
Alleles , Arabs/genetics , Diabetes Mellitus, Type 1/genetics , Genetic Predisposition to Disease , HLA-DQ Antigens/genetics , HLA-DR Antigens/genetics , Haplotypes , Adolescent , Adult , Bahrain , Child , Cross-Sectional Studies , Female , Gene Frequency , Genotype , HLA-DQ beta-Chains , HLA-DRB1 Chains , Humans , Lebanon , Male , Retrospective StudiesABSTRACT
OBJECTIVE: Children and adolescent patients with type 1 diabetes mellitus (T1DM) may have an increased risk of developing diabetic nephropathy (DNP). The incidence of DNP varies with glycemic control, and peaks after 15-20 years of diabetes and decline thereafter. Microalbuminuria is uncommon before puberty, and usually occurs after 5 years of diabetic duration. Once overt DNP is established, a progressive decline in the glomerular filtration rate and elevation in arterial blood pressure occurs, and it is the most important disorder leading to renal failure in adult patients with diabetes in developed countries. The purpose of this study was to screen all the children and adolescent with T1DM of 5 years duration or more for DNP. METHODS: Between April 2000 and February 2001, all patients with T1DM of more than 5 years, who were diagnosed between years 1985 to 1995 and followed by pediatricians at Salmaniya Medical Complex, Kingdom of Bahrain, were screened for DNP. Medical records were reviewed for demographical data, blood for hemoglobin A1c (HbA1c), fasting sugar and renal function test. The presence of DNP, retinopathy and neuropathy and the medications were also reviewed. DNP was diagnosed by urine microscopy, overnight urine collection for albumin to creatinine ratio, or 24-hour urine for protein, and the medications RESULTS: Diabetic nephropathy was diagnosed in 10 patients (31%), 2 with microalbuminuria (incipient nephropathy), and 8 with proteinuria (clinical nephropathy). Diabetic nephropathy was diagnosed at a mean of 10.5 years after the onset of T1DM. The mean age was 18 years for the DNP. Mean HbA1c was 11.8% for DNP and 10.2% for non-nephropathy group. All the patients with DNP were treated with an angiotensin converting enzyme inhibitor, 5 of them had hypertension. None developed renal failure or retinopathy. CONCLUSION: Microalbuminuria is uncommon before 5 years of the onset of T1DM. Screening for microalbuminuria should be performed in adolescent over 12 years of age, with diabetes of more than 5 years duration and persistent hyperglycemia (HbA1c > 11 %).
