ABSTRACT
The transcription factor 7-like 2 (TCF7L2) rs7903146 T allele was associated with type 2 diabetes (T2D) in most populations worldwide. In individuals of European descent, the association with T2D was recently found to be modulated by obesity status. However, further studies are necessary to clarify if whether interaction exists among subjects of non-European descent. In the present study, we analyzed the association of rs7903146 with T2D in 90 nonobese (Body Mass Index [BMI] <25kg/m(2)), 171 overweight (25≤BMI<30kg/m(2)) et 98 obese (BMI≥30kg/m(2)) individuals from Tunisia. The T allele was nominally associated with T2D in nonobese subjects (Odds Ratio [OR]=3.24 [1.10-9.53], P=0.021) whereas no effect was detected in overweight (P=0.3) and obese (P=0.22) individuals. Consequently, the same risk allele decreased susceptibility to obesity in T2D subjects (OR=0.47 [0.23-0.94], P=0.029) but not in normoglycemic controls (P=0.44). When analyzed all together, no allelic association was observed with T2D (P=0.20) whereas an artefactual association with decreased obesity (0.59 [0.38-0.90], P=0.013) was detected. As in Europeans, TCF7L2 is therefore not a risk factor for obesity in Tunisians, but its effect on T2D risk is modulated by obesity. In conclusion, the TCF7L2 rs7903146 T allele is nominally associated with T2D susceptibility in nonobese individuals from Tunisia.
Subject(s)
Diabetes Mellitus, Type 2/genetics , Polymorphism, Single Nucleotide , Transcription Factor 7-Like 2 Protein/genetics , Adult , Aged , Alleles , Blood Glucose/analysis , Body Mass Index , Comorbidity , Diabetes Mellitus, Type 2/epidemiology , Female , Gene Frequency , Genotype , Humans , Ideal Body Weight , Male , Middle Aged , Obesity/epidemiology , Overweight/epidemiology , Prevalence , Risk Factors , Transcription Factor 7-Like 2 Protein/physiology , Tunisia/epidemiologyABSTRACT
Several studies of the association between HLA and type 1 diabetes have been carried out revealing differences between ethnic groups. Our study, as part of the studies that should be performed about this association in the rest of the word, aims at elucidating the HLA DRB1, DQB1 polymorphism in Tunisian type 1 diabetes. This study includes 43 unrelated type 1 diabetes patients, and their mean age at onset is less than 15 years. Analysis of the frequency of alleles and haplotypes in these subjects, compared to a reference group (n = 101) led to the following results. 1) The Tunisian insulin-dependent diabetics present similarities as well as differences with other ethnic groups (Caucasians, North Africans). 2) The haplotype DRB1*04 DQ*0302 and DRB1*03 DQB1*0201 is positively associated to type 1 diabetes. 3) The heterozygotic genotype DRB1*04 DQB1*0302 / DRB1*03 DQB1*0201 is strongly associated to type 1 diabetes. 4) The haplotypes DRB1*01501 DQB1*0602 and DRB1*11 DQB1*0301 proved to be protective. In addition, the study of the subtypes DRB1*04 showed that alleles DRB1*0405 predispose to type 1 diabetes, whereas the allele DRB1*0403, which is in linkage disequilibrium with the DQB1*0402 in the Tunisian population, has a protective effect.
