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Transcription factor 7-like2 (TCF7L2) gene has been associated with type 2 diabetes in different ethnic groups. As TCF7L2 gene is involved in regulation of insulin secretion, we hypothesized that TCF7L2 gene variants may be associated with MODY. We examined the role of rs12255372(G/T) and rs7903146(C/T) polymorphisms of TCF7L2 gene in MODY, early-onset type 2 diabetes (EO-T2DM), late-onset type 2 diabetes (LO-T2DM), type 1 diabetes (T1DM) and normal glucose tolerant (NGT) Asian Indians. Subjects were selected from the Chennai Urban Rural Epidemiology Study, a population based study in south India (EO-T2DM, LO-T2DM and NGT) and a tertiary diabetes centre (MODY and TIDM). 136 MODY subjects with autosomal dominant inheritance (age at onset(AAO) <25years), 397 EO-T2DM (AAO:25-40years), 738 LO-T2DM (AAO:>40years), 174 T1DM and 996 NGT subjects were studied. Genotyping of the two polymorphisms was carried out using PCR-RFLP and confirmed by direct sequencing. Frequency of the 'T' allele of rs12255372 and rs7903146 was significantly higher in MODY (30%,p=0.00001 and 45%,p<0.00001 respectively) and EO-T2DM (25%,p=0.0004; 37%,p<0.00001) compared to NGT (19%;28%). Odds ratios (OR) for GT and TT genotypes of the rs12255372 were higher in the MODY (OR:l.53,p=0.032 and 3.77,p=0.00002 respectively) and EO-T2DM (OR:1.48,p=0.002 and 1.75,p=0.034) compared to GG. The OR for CT and TT genotypes of rs7903146 were higher in MODY (OR:2.73,p<0.00001 and 4.10,p<0.00001 respectively) and EO-T2DM (OR: 1.71,p=0.00002 and 1.94,p=0.001) compared to CC. The CT genotype of rs7903146 showed association with LO-T2DM (OR: 1.26,p=0.022 compared to CC) but the TT genotype did not show any association. There was no association of rs12255372 with LO-T2DM and both polymorphisms were not associated with T1DM. Among Asian Indians, rs12255372(G/T) and rs7903146(C/T) polymorphisms of TCF7L2 gene are more strongly associated with MODY and EOT2DM and rs7903146 less strongly with LO-T2DM, while both polymorphisms are not associated with T1DM. [ABSTRACT FROM AUTHOR]

We and others in a variety of ethnic groups have previously described associations of various SNPs of the uncoupling protein genes UCP2 and UCP3 (located within 17 kb of each other on chromosome 11q13) with both central fat disposition and BMI. The aim of this study was to do a replication study in South Indian subjects using a family based approach and selecting SNP's by' a priori hypothesis' defined by a previous association with obesity/waits in other studies and/or functional data. Five SNPs were studied; 1 by Ampliflour (UCP2-866 rs659366), 1 by SNAPSHOT (UCP3Y210Y rs2075577), 2 by TaqMan (UCP3-55 rs1800849, UCP2 A55V rs660339) and one by PCR-RFLP (UCP2 exon 8 INDEL) in 882 South Indian participants from 236 families ascertained from community based study of healthy families living in Chennai, India. Statistical analysis was performed using SOLAR and anthropometric variables were corrected for age and sex. The QTLD analysis showed the BMI was associated to the UCP3 rs1800849 (AA 23.9±0.29, AB 23.5±0.32, BB 23.0±0.5, p=0.027) and UCP3 rs2075577 (AA 24.6±0.37, AB 24.0±0.30, BB 23.4±0.39, p=0.022). Waist circumference to the UCP2 rs660339 (AA 84.3±0A8, AB 85.1±0.41, BB 85.9±0.65, p=0.028). Body fat percentage to UCP2 rs660339 (AA 22.9±0.31, AB 23.2±0.27, BB 23.5±0.42, p=0.048) and UCP2 rs659366 (AA 22.7±0.31, AB 22.9±0.26, BB 23.27±0.41, p=0.076). This detailed analysis confirms associations between anthropometric traits and the UCP2/UCP3 locus but that separate SNPs are associated with either BMI or fat distribution. [ABSTRACT FROM AUTHOR]