| Objective:As we know, both genetic background and environmental factors involve in development of type2diabetes (T2DM).The main pathophysiological changes in T2DM are impaired insulin secretion and insulin resistence,so genes which involve in insulin secretion or insulin signaling are important candidate genes for T2DM.R type calcium channel Cav2.3is considered responsible for sustained second-phase insulin release.Gene polymorphisms in CACNAIE which encodes Cav2.3can lead to disfunction of insulin secretion.Retinoid binding protein4(RBP4)and its gene polymorphisms are proved to be associated with type2diabetes in different races. Stimulated by Retinoic Acid gene homolog6(STRA6) is the high affinity cell surface receptor for RBP4. It is found recently that STRA6not only is a vitamin A transporter but also is a cell-surface signaling receptor which can mediate the signaling cascade that can lead to insulin resistance. We explore the association of SNPs rsl99925in CACNAIE and rs974456in STRA6with type2diabetes in Tianjin Han Chinese population.Methods:A total of604subjects were enrolled according to OGTT, including292cases with T2DM,190cases with impaired glucose regulation (IGR) and122cases with normal glucose tolerance (NGT).After an overnight fasting, all subjects’ venous blood was drawn for DNA extraction and measurement of biochemistry parameters.We detected CACNAIE rs199925and STRA6rs974456polymorphisms by PCR-RFLP and DNA sequencing. Insulin resistance (IR) was estimated according to HOMA-IR and ISI. β cell function was measured according to HOMA-β, MBCI, ΔI30/ΔG30, ΔI120/ΔG120and area under curve of insulin(AUCI), and deposition index(DI3o,DI12o,DI-HOMA) were also measured. Statistical analysis was done in SPSS17.0software.Results:(1) The genotype distribution of CACNAIE rs199925and STRA6rs974456met Hardy-Weinberg principal.(2)Frequencies of TT,GT and GG genotype of CACNAIE rsl99925were61.5%,32%,6.6%in NGT group,63.2%,31.6%,5.3%in IGR group,and44.9%,41.1%,14%in T2DM group respectively. Frequencies of risk allele G in NGT, IGR and T2DM group were22.5%,21.1%and34.6%respectively. There was significant difference in genotype and allele distribution between T2DM and NGT or IGR group (P<0.017). The diabetes risk for CACNA1E rs199925G allele carrier was1.7fold of the T allele carrier.p cell function(HOMA-p, MBCI, ΔI30/ΔG30, ΔI120/ΔG120, AUC1) and deposition index(DI30, DI120, DI-HOMA) gradually decreased in TT, GT and GG genotype(P<0.05). We failed to find significant difference in IR among three genotypes (P>0.05).(3)Frequencies of CC,CT and TT genotype of STRA6rs974456were57.4%,36.9%,5.7%in NGT group,54.2%,38.4%,7.4%in IGR group,and43.8%,41.1%,15.1%in T2DM group respectively. Frequencies of risk allele T in NGT, IGR and T2DM group were43.8%,41.1%and15.1%respectively. There was significant difference in genotype and allele distribution between T2DM and NGT or IGR group (P<0.017). The diabetes risk for STRA6rs974456T allele carrier was1.6fold of the C allele carrier.Deposition index (DI30, DI120) gradually decreased in CC, CT and TT genotype (P<0.05). We failed to find significant difference in β cell function and IR among three genotypes (P>0.05).(4)Logistic regression showed that CACNA1E rs199925GG genotype(OR=2.531,95%CI:1.148-4.972,P=0.002) and G allele(OR=1.746,95%CI:1.109-3.715,P=0.007), STRA6rs974456TT genotype (OR=1.811,95%CI:1.179-3.052,P=0.015) and T allele(OR=1.604,95%CI:1.253-2.054,.P=0.000), TG, LDL-C were independent risk factors for T2DM;HOMA-P and DI30were protective factors.Conclusions:(1)CACNA1E rs199925and STRA6rs974456polymorphisms existed in Tianjin Han population.(2)The polymorphism of CACNA1E rs199925was associated with impaired beta cell function. CACNA1E gene was susceptibility gene of T2DM.(3)The polymorphism of STRA6rs974456was associated with the decrease of DI30and DI120.STRA6gene was susceptibility gene of T2DM.(4)CACNA1E rs199925GG genotype and G allele,STRA6rs974456TT genotype and T allele,TG and LDL-C were independent risk factors for T2DM;HOMA-β and DI30were protective factors. |
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