RESUMO
We investigated the impact of gender on T2DM association with confirmed susceptibility loci. CDKN2A/2B rs10811661, KCNJ11 rs5219, and TCF7L2 rs7903146 were associated with T2DM in females, while POLI rs488846 was associated with T2DM among males; the association of SLC30A8 rs13266634 and TCF7L2 rs4506565, rs12243326, and rs12255372 with T2DM was gender-independent.
Assuntos
Diabetes Mellitus Tipo 2/genética , Polimorfismo de Nucleotídeo Único/genética , Proteínas/genética , Árabes/genética , Biomarcadores/análise , Estudos de Casos e Controles , Proteínas de Transporte de Cátions/genética , Inibidor de Quinase Dependente de Ciclina p15/genética , Inibidor p16 de Quinase Dependente de Ciclina/genética , DNA Polimerase I/genética , Feminino , Seguimentos , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Canais de Potássio Corretores do Fluxo de Internalização/genética , Prognóstico , Fatores Sexuais , Proteína 2 Semelhante ao Fator 7 de Transcrição/genética , Tunísia , Transportador 8 de ZincoRESUMO
AIMS: Polymorphisms of KCNQ1 were previously associated with type 2 diabetes (T2DM) in select Caucasian and non-Caucasian populations. We investigated the association of rs231361, rs231359, rs151290, rs2237892, rs2283228, rs2237895, and rs2237896 KCNQ1 polymorphisms with T2DM in Tunisian Arabs. SUBJECTS AND METHODS: Subjects comprised 900 T2DM patients and 600 normoglycemic controls. KCNQ1 genotyping was done by allelic discrimination (real-time PCR) and PCR-RFLP methods; the contribution of KCNQ1 polymorphisms to T2DM were analyzed by Haploview and regression analysis. RESULTS: Minor allele frequency (MAF) of the 7 tested KCNQ1 variants was comparable between T2DM cases and controls. Mild association of rs2237892 genotypes with T2DM was seen (P=0.014), highlighted by the significant association of the C/T genotype with increased T2DM risk (OR, 2.11; 95%CI, 1.25-3.53), after adjusting for BMI, gender, systolic and diastolic blood pressure, and serum lipid profile. Heterogeneity in linkage disequilibrium pattern between tested KCNQ1 variants analyzed was seen. Two-locus (rs231361 and rs231359) and 5-locus (remaining 5 SNPs) haplotype analysis did not reveal any significant association with any of the haplotypes contained in either block 1 or block 2. CONCLUSION: These results indicate that there was no evidence for an association of KCNQ1 polymorphisms with T2DM in Tunisian Arabs.
