PMID- 33996288 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220423 IS - 2167-8359 (Print) IS - 2167-8359 (Electronic) IS - 2167-8359 (Linking) VI - 9 DP - 2021 TI - TCF7L2 rs7903146 polymorphism association with diabetes and obesity in an elderly cohort from Brazil. PG - e11349 LID - 10.7717/peerj.11349 [doi] LID - e11349 AB - BACKGROUND: Type 2 diabetes mellitus (T2DM) and obesity are complex pandemic diseases in the 21st century. Worldwide, the T allele rs7903146 in the TCF7L2 gene is recognized as a strong GWAS signal associated with T2DM. However, the association between the C allele and obesity is still poorly explored and needs to be replicated in other populations. Thus, the primary objectives of this study were to evaluate the TCF7L2 rs7903146 association with T2DM according to BMI status and to determine if this variant is related to obesity and BMI variation in a cohort of elderly Brazilians. METHODS: A total of 1,023 participants from an elderly census-based cohort called SABE (Saude, Bem Estar e Envelhecimento-Health, Well-Being and Aging) were stratified by BMI status and type 2 diabetes presence. The TCF7L2 genotypes were filtered from the Online Archive of Brazilian Mutations (ABraOM-Online Archive of Brazilian Mutations) database, a web-based public database with sequencing data of samples of the SABE's participants. Logistic regression models and interaction analyses were performed. The BMI variation (∆BMI) was calculated from anthropometric data collected in up to two time-points with a ten-year-assessment interval. RESULTS: The association between the rs7903146 T allele and T2DM was inversely proportional to the BMI status, with an increased risk in the normal weight group (OR 3.36; 95% CI [1.46-7.74]; P = 0.004). We confirmed the T allele association with risk for T2DM after adjusting for possible confound ing variables (OR 2.35; 95% CI [1.28-4.32]; P = 0.006). Interaction analysis showed that the increased risk for T2DM conferred by the T allele is modified by BMI (P (interaction) = 0.008), age (P (interaction) = 0.005) and gender (P (interaction) = 0.026). A T allele protective effect against obesity was observed (OR 0.71; 95% CI [0.54-0.94]; P = 0.016). The C allele increased obesity risk (OR 1.40; 95% CI [1.06-1.84]; P = 0.017) and the CC genotype showed a borderline association with abdominal obesity risk (OR 1.28; 95% CI [1.06-1.67]; P = 0.045). The CC genotype increased the obesity risk factor after adjusting for possible confounding variables (OR 1.41; 95% CI [1.06-1.86]; P = 0.017). An increase of the TT genotype in the second tertile of ∆BMI values was observed in participants without type 2 diabetes (OR 5.13; 95% CI [1.40-18.93]; P = 0.009) in the recessive genetic model. CONCLUSION: We confirmed that the rs7903146 is both associated with T2DM and obesity. The TCF7L2 rs7903146 T allele increased T2DM risk in the normal weight group and interacted with sex, age and BMI, while the C allele increased obesity risk. The TT genotype was associated with a lesser extent of BMI variation over the SABE study's 10-year period. CI - (c) 2021 Bride et al. FAU - Bride, Lais AU - Bride L AD - Biotechnology Graduate Program, Federal University of Espirito Santo, Vitoria, Espirito Santo, Brazil. FAU - Naslavsky, Michel AU - Naslavsky M AUID- ORCID: 0000-0002-9068-1713 AD - Biosciences Institute, University of Sao Paulo, Sao Paulo, Sao Paulo, Brazil. FAU - Lopes Yamamoto, Guilherme AU - Lopes Yamamoto G AD - Biosciences Institute, University of Sao Paulo, Sao Paulo, Sao Paulo, Brazil. FAU - Scliar, Marilia AU - Scliar M AD - Biosciences Institute, University of Sao Paulo, Sao Paulo, Sao Paulo, Brazil. FAU - Pimassoni, Lucia Hs AU - Pimassoni LH AUID- ORCID: 0000-0002-1240-4008 AD - School of Science of Santa Casa de Misericordia de Vitoria, Vitoria, Espirito Santo, Brazil. FAU - Sossai Aguiar, Paola AU - Sossai Aguiar P AD - Biotechnology Graduate Program, Federal University of Espirito Santo, Vitoria, Espirito Santo, Brazil. FAU - de Paula, Flavia AU - de Paula F AUID- ORCID: 0000-0001-8679-2982 AD - Biotechnology Graduate Program, Federal University of Espirito Santo, Vitoria, Espirito Santo, Brazil. AD - Department of Biological Sciences, Federal University of Espirito Santo, Vitoria, Espirito Santo, Brazil. FAU - Wang, Jaqueline AU - Wang J AD - Biosciences Institute, University of Sao Paulo, Sao Paulo, Sao Paulo, Brazil. FAU - Duarte, Yeda AU - Duarte Y AD - School of Nursing, University of Sao Paulo, Sao Paulo, Sao Paulo, Brazil. AD - School of Public Health, University of Sao Paulo, Sao Paulo, Sao Paulo, Brazil. FAU - Passos-Bueno, Maria Rita AU - Passos-Bueno MR AD - Biosciences Institute, University of Sao Paulo, Sao Paulo, Sao Paulo, Brazil. FAU - Zatz, Mayana AU - Zatz M AD - Biosciences Institute, University of Sao Paulo, Sao Paulo, Sao Paulo, Brazil. FAU - Imbroisi Valle Errera, Flavia AU - Imbroisi Valle Errera F AUID- ORCID: 0000-0002-8069-6372 AD - Biotechnology Graduate Program, Federal University of Espirito Santo, Vitoria, Espirito Santo, Brazil. AD - Department of Biological Sciences, Federal University of Espirito Santo, Vitoria, Espirito Santo, Brazil. LA - eng PT - Journal Article DEP - 20210505 PL - United States TA - PeerJ JT - PeerJ JID - 101603425 PMC - PMC8106398 OTO - NOTNLM OT - BMI OT - Obesity OT - TCF7L2 OT - Type 2 diabetes OT - rs7903146 COIS- The authors declare that they have no competing interests. EDAT- 2021/05/18 06:00 MHDA- 2021/05/18 06:01 PMCR- 2021/05/05 CRDT- 2021/05/17 06:12 PHST- 2020/10/27 00:00 [received] PHST- 2021/04/04 00:00 [accepted] PHST- 2021/05/17 06:12 [entrez] PHST- 2021/05/18 06:00 [pubmed] PHST- 2021/05/18 06:01 [medline] PHST- 2021/05/05 00:00 [pmc-release] AID - 11349 [pii] AID - 10.7717/peerj.11349 [doi] PST - epublish SO - PeerJ. 2021 May 5;9:e11349. doi: 10.7717/peerj.11349. eCollection 2021.