ARHGEF11基因R1467H多态性与甘肃回族、汉族2型糖尿病的相关性研究
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摘要
目的
明确ARHGEF11基因R1467H位点多态性在甘肃回、汉两民族人群中的分布及其差异性；初步探讨甘肃回、汉族人群ARHGEF11基因R1467H位点多态性与2型糖尿病、胰岛素抵抗、肥胖及血脂异常的相关性。
方法
1.采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)和DNA直接测序技术,分别对回族117例2型糖尿病患者(T2DM组)、104例正常对照者(NC组)和汉族149例2型糖尿病患者(T2DM组)、114例正常对照者(NC组)ARHGEF11基因R1467H多态性位点进行基因分型,并分析回、汉族人群两组基因型和等位基因频率的差异。
2.采用全自动生化分析仪测定空腹血糖(FPG)、血脂、肝功能、肾功能,糖化血红蛋白分析仪测定糖化血红蛋白(HbA1c),放射免疫法测定空腹胰岛素(FINS)。
3.同时测量身高、体重、血压、腰围、臀围,计算体重指数(BMI)=体重／身高2(Kg／m2),腰臀比(WHR)=腰围／臀围,HOMA胰岛素抵抗指数(HOMA-IR)=空腹血糖(FPG)×空腹胰岛素(FINS)／22.5。
结果
1.回、汉族人群2型糖尿病组间以及回、汉族人群正常对照组间ARHGEF11基因R1467H位点基因型频率和等位基因频率比较均无统计学差异(P>0.05)。
2.汉族人群2型糖尿病组和正常对照组的基因型GG、GA、AA频率分别为61.1%、35.6%、3.3%和75.4%、21.1%、3.5%,等位基因G、A频率在两组间分别为78.9%、21.1%和86.0%、14.0%,汉族人群2型糖尿病组基因型和等位基因频率分布与正常对照组比较差异均有统计学意义(P<0.05)；回族人群2型糖尿病组和正常对照组的基因型GG、GA、AA频率分别为50.4%、43.6%、6.0%和66.3%、28.8%、4.8%,等位基因G、A频率在两组间分别为72.2%、27.8%和80.8%、19.2%,回族人群2型糖尿病组基因型和等位基因频率分布与正常对照组比较差异均有统计学意义(P<0.05)。
3.汉族人群GA基因型患2型糖尿病的风险显著高于GG基因型(OR=2.087,95% CI.1.186-3.673,P=0.010),且A等位基因能够显著增加2型糖尿病的患病风险(OR=1.642,95% CI：1.031-2.616,P=0.036)；回族人群GA基因型在2型糖尿病人群中的频率高于GG基因型,是2型糖尿病的危险因素(OR,1.988；95%CI,1.125-3.513,P=0.017),2型糖尿病组中A等位基因能够增加2型糖尿病的患病风险(OR,1.615；95%CI,1.032-2.528,P=0.035)。
4.汉族人群2型糖尿病组A等位基因携带者(即GA+AA基因型)较GG基因型有更高的空腹血糖、空腹胰岛素和胰岛素抵抗指数(P＜0.05)；汉族人群正常对照组空腹血糖水平在A等位基因携带者中高于GG基因型,差异有统计学意义(P<0.05)；回族人群2型糖尿病组A等位基因携带者较GG基因型有更高的空腹血糖水平(P=0.002)；在回族对照组中,A等位基因携带者的腰臀比和低密度脂蛋白胆固醇水平高于GG基因型,差异有统计学意义(P<0.05)。
结论
ARHGEF11基因R1467H位点多态性在甘肃回族和汉族人群中的分布不存在差异；ARHGEF11基因R1467H位点多态性可能与甘肃汉族人群胰岛素抵抗及2型糖尿病相关,亦可能与甘肃回族人群2型糖尿病、肥胖及血脂异常相关。
Objectives The aim of our study was to investigate the distribution and difference of ARHGEF11 gene R1467H polymorphism in Hui and Han population in Gansu province. To evaluate the relationship between the R1467H polymorphism in ARHGEF11 and risk of type 2 diabetes mellitus (T2DM) and insulin resistance in Hui and Han population in Gansu province.
Methods We genotyped R1467H polymorphism in 117 patients with T2DM and 104 control subjects in Gansu Hui population and 149 patients with T2DM and 114 control subjects in Gansu Han population, using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) protocol and DNA sequencing methods. The frequencies of genotypes and alleles at the site were compared between the T2DM and control groups. Total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and fasting blood glucose levels were determined by automatic biochemistry analyzer. Glycosylated hemoglobin (HbAlc) value was determined by HbAlc analyzer. Fasting insulin concentration was measured using insulin radioimmunoassay kit. At the same time, we measured the height, weight, waist circumference, hip circumference, blood pressure. The body mass index (BMI), waist hip ratio (WHR) and insulin resistance index (HOMA-IR) were computed.
Results (1) There was no significant difference in distribution of genotype and allele in R1467H polymorphism between T2DM and NC in Hui and Han population of Gansu province. (P>0.05); (2) Genotype frequencies of GG, GA, AA were 61.1%, 35.6%,3.3%in T2DM group and 75.4%,21.1%,3.5%in NC group, allele frequencies of G, A were 78.9%,21.1%in T2DM group and 86.0%,14.0%in NC group in Han population. Genotype frequencies of GG, GA, AA were50.4%,43.6%, 6.0%in T2DM group and 66.3%,28.8%,4.8%in NC group, allele frequencies of G, A were 72.2%,27.8%in T2DM group and 80.8%,19.2%in NC group in Hui population. There was a significant difference in distribution of genotype and allele in R1467H polymorphism between T2DM and NC in Han and Hui population; (3) The relative risk of GA genotype in the T2DM of Han population was significantly higher than GG genotype (OR=2.087,95% CI:1.186-3.673, P= 0.010). And A allele was associated with increased risk of T2DM (OR= 1.642,95% CI:1.031-2.616, P= 0.036). The relative risk of GA genotype in the T2DM of Hui population was significantly higher than GG genotype (OR,1.988; 95% CI,1.125-3.513, P= 0.017). And A allele was associated with increased risk of T2DM (OR,1.6.15; 95%CI, 1.032-2.528, P= 0.035); (4) In Han population, the levels of FPG, FINS and HOMA-IR in the type 2 diabetes group of Han population were higher in A allele carriers (GA+AA genotype) than those of GG genotype (all P< 0.05). The level of FPG in the NC group was significantly higher in genotypes with allele A than in GG genotype (P< 0.05). In Hui population, the level of FPG in the type 2 diabetes group was significantly higher in GA+AA genotype than in GG genotype (P= 0.002). In the NC group, the subjects carrying GA, AA genotype had the significant increased levels of WHR and LDL-C (P< 0.05).
Conclusion There was no significant difference in distribution of ARHGEF11 R1467H polymorphism between T2DM and NC in Hui and Han population of Gansu province. Our investigation suggests that the R1467H polymorphism of ARHGEF11 gene may contribute to susceptibility to T2DM and insulin resistance in Han population in Gansu province. Moreover, the SNP was likely related to increased risk of T2DM, obesity and dyslipidemia in Hui population in Gansu province.
明确ARHGEF11基因R1467H位点多态性在甘肃回、汉两民族人群中的分布及其差异性；初步探讨甘肃回、汉族人群ARHGEF11基因R1467H位点多态性与2型糖尿病、胰岛素抵抗、肥胖及血脂异常的相关性。
方法
1.采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)和DNA直接测序技术,分别对回族117例2型糖尿病患者(T2DM组)、104例正常对照者(NC组)和汉族149例2型糖尿病患者(T2DM组)、114例正常对照者(NC组)ARHGEF11基因R1467H多态性位点进行基因分型,并分析回、汉族人群两组基因型和等位基因频率的差异。
2.采用全自动生化分析仪测定空腹血糖(FPG)、血脂、肝功能、肾功能,糖化血红蛋白分析仪测定糖化血红蛋白(HbA1c),放射免疫法测定空腹胰岛素(FINS)。
3.同时测量身高、体重、血压、腰围、臀围,计算体重指数(BMI)=体重／身高2(Kg／m2),腰臀比(WHR)=腰围／臀围,HOMA胰岛素抵抗指数(HOMA-IR)=空腹血糖(FPG)×空腹胰岛素(FINS)／22.5。
结果
1.回、汉族人群2型糖尿病组间以及回、汉族人群正常对照组间ARHGEF11基因R1467H位点基因型频率和等位基因频率比较均无统计学差异(P>0.05)。
2.汉族人群2型糖尿病组和正常对照组的基因型GG、GA、AA频率分别为61.1%、35.6%、3.3%和75.4%、21.1%、3.5%,等位基因G、A频率在两组间分别为78.9%、21.1%和86.0%、14.0%,汉族人群2型糖尿病组基因型和等位基因频率分布与正常对照组比较差异均有统计学意义(P<0.05)；回族人群2型糖尿病组和正常对照组的基因型GG、GA、AA频率分别为50.4%、43.6%、6.0%和66.3%、28.8%、4.8%,等位基因G、A频率在两组间分别为72.2%、27.8%和80.8%、19.2%,回族人群2型糖尿病组基因型和等位基因频率分布与正常对照组比较差异均有统计学意义(P<0.05)。
3.汉族人群GA基因型患2型糖尿病的风险显著高于GG基因型(OR=2.087,95% CI.1.186-3.673,P=0.010),且A等位基因能够显著增加2型糖尿病的患病风险(OR=1.642,95% CI：1.031-2.616,P=0.036)；回族人群GA基因型在2型糖尿病人群中的频率高于GG基因型,是2型糖尿病的危险因素(OR,1.988；95%CI,1.125-3.513,P=0.017),2型糖尿病组中A等位基因能够增加2型糖尿病的患病风险(OR,1.615；95%CI,1.032-2.528,P=0.035)。
4.汉族人群2型糖尿病组A等位基因携带者(即GA+AA基因型)较GG基因型有更高的空腹血糖、空腹胰岛素和胰岛素抵抗指数(P＜0.05)；汉族人群正常对照组空腹血糖水平在A等位基因携带者中高于GG基因型,差异有统计学意义(P<0.05)；回族人群2型糖尿病组A等位基因携带者较GG基因型有更高的空腹血糖水平(P=0.002)；在回族对照组中,A等位基因携带者的腰臀比和低密度脂蛋白胆固醇水平高于GG基因型,差异有统计学意义(P<0.05)。
结论
ARHGEF11基因R1467H位点多态性在甘肃回族和汉族人群中的分布不存在差异；ARHGEF11基因R1467H位点多态性可能与甘肃汉族人群胰岛素抵抗及2型糖尿病相关,亦可能与甘肃回族人群2型糖尿病、肥胖及血脂异常相关。
Objectives The aim of our study was to investigate the distribution and difference of ARHGEF11 gene R1467H polymorphism in Hui and Han population in Gansu province. To evaluate the relationship between the R1467H polymorphism in ARHGEF11 and risk of type 2 diabetes mellitus (T2DM) and insulin resistance in Hui and Han population in Gansu province.
Methods We genotyped R1467H polymorphism in 117 patients with T2DM and 104 control subjects in Gansu Hui population and 149 patients with T2DM and 114 control subjects in Gansu Han population, using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) protocol and DNA sequencing methods. The frequencies of genotypes and alleles at the site were compared between the T2DM and control groups. Total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and fasting blood glucose levels were determined by automatic biochemistry analyzer. Glycosylated hemoglobin (HbAlc) value was determined by HbAlc analyzer. Fasting insulin concentration was measured using insulin radioimmunoassay kit. At the same time, we measured the height, weight, waist circumference, hip circumference, blood pressure. The body mass index (BMI), waist hip ratio (WHR) and insulin resistance index (HOMA-IR) were computed.
Results (1) There was no significant difference in distribution of genotype and allele in R1467H polymorphism between T2DM and NC in Hui and Han population of Gansu province. (P>0.05); (2) Genotype frequencies of GG, GA, AA were 61.1%, 35.6%,3.3%in T2DM group and 75.4%,21.1%,3.5%in NC group, allele frequencies of G, A were 78.9%,21.1%in T2DM group and 86.0%,14.0%in NC group in Han population. Genotype frequencies of GG, GA, AA were50.4%,43.6%, 6.0%in T2DM group and 66.3%,28.8%,4.8%in NC group, allele frequencies of G, A were 72.2%,27.8%in T2DM group and 80.8%,19.2%in NC group in Hui population. There was a significant difference in distribution of genotype and allele in R1467H polymorphism between T2DM and NC in Han and Hui population; (3) The relative risk of GA genotype in the T2DM of Han population was significantly higher than GG genotype (OR=2.087,95% CI:1.186-3.673, P= 0.010). And A allele was associated with increased risk of T2DM (OR= 1.642,95% CI:1.031-2.616, P= 0.036). The relative risk of GA genotype in the T2DM of Hui population was significantly higher than GG genotype (OR,1.988; 95% CI,1.125-3.513, P= 0.017). And A allele was associated with increased risk of T2DM (OR,1.6.15; 95%CI, 1.032-2.528, P= 0.035); (4) In Han population, the levels of FPG, FINS and HOMA-IR in the type 2 diabetes group of Han population were higher in A allele carriers (GA+AA genotype) than those of GG genotype (all P< 0.05). The level of FPG in the NC group was significantly higher in genotypes with allele A than in GG genotype (P< 0.05). In Hui population, the level of FPG in the type 2 diabetes group was significantly higher in GA+AA genotype than in GG genotype (P= 0.002). In the NC group, the subjects carrying GA, AA genotype had the significant increased levels of WHR and LDL-C (P< 0.05).
Conclusion There was no significant difference in distribution of ARHGEF11 R1467H polymorphism between T2DM and NC in Hui and Han population of Gansu province. Our investigation suggests that the R1467H polymorphism of ARHGEF11 gene may contribute to susceptibility to T2DM and insulin resistance in Han population in Gansu province. Moreover, the SNP was likely related to increased risk of T2DM, obesity and dyslipidemia in Hui population in Gansu province.
引文
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