| Objective:The study aimed at investigating the association between the single nucleotide polymorphisms(SNPs)of the gene ADP-ribosylation-like factor 15(ARL15)with type 2 diabetes mellitus(T2DM)and macroangiopathy in Korean and Han ethnic nationality of Yanbian area in China.Methods:This was a case-control study including 99 T2DM patients,157 T2DM with macroangiopathy patients and 174 controls.LDR was carried to detect the rs255758 and SnaPshot(?)Multiple was carried to detect the rs4311394 of the gene ARL15.Enzyme-linked immunosorbent assay(ELISA)was carried to detect the protein expression of Q9NXU5(ARL15)and insulin(INA).Anthropometric indices of high density lipoprotein(HDL-C),fasting blood glucose(FPG),total cholesterol(TC),low density lipoprotein(LDL-C),triglyceride(TG)and serum creatinine(SCr)were measured.The color Doppler was carried to detect carotid artery intima media thickness(IMT).All samples were required testing height,weight,waist circumference,hip circumference,blood pressure and body fat percentage(BFP).The body mass index(BMI)calculated with equation that incorporates height and weight.The waist and hip were measured,we then calculated waist-hip ratio.Results:1.In this study we tested allele frequency and genotype frequency for rs255758,rs4311394 in Korean nationality controls and Han nationality controls from Yanbian,which suggested that the C allele frequency for rs255758 is lower in Korean nationality controls than Han nationality controls,but there were no significant difference(p>0.05)and the genotype frequency for rs255758 did not exhibit significant difference in Korean nationality controls and Han nationality controls(p>0.05).However G allele frequency and GG genotype frequency for rs4311394 were higher in Korean nationality controls than Han nationality controls,but they did not exhibit significant difference(p>0.05).2.Multidimensional scaling analysis did not reveal allele frequency and genotype frequency for rs255758,rs4311394 were distinct in patients and controls(p>0.05).3.We found 4 haplotypes,they did not exhibit significant difference in T2DM patients and controls(p>0.05).We have also identified the 4 haplotypes above were not distinct in T2DM with macroangiopathy patients and controls(p>0.05).4.We then tested whether combine genotype were associated with T2DM and T2DM with macroangiopathy,which suggested that the combine genotype AA-AG frequency was higher in T2DM patients than controls(P=0.08,OR=0.68,95%CI:0.41-1.13),however the combine genotype AC-AG frequency was lower in T2DM with macroangiopathy patients than controls(P=0.07,OR=0.56,95%CI:0.28-1.11).5.In controls,the protein expression of ARL15 was higher in Korean nationality than Han nationality(45.07±13.17>38.64±6.05,P=0.07).In Korean T2DM patients the level of WHR,BMI,FPG,TC,LDL-C,BFP,IR,INA were raised and correlate with disease severity.However the level of TG was lower in Korean T2DM patients than Korean T2DM with macroangiopathy patients(p<0.05).We have also identified the level of WHR?FPG,TC,TG,LDL-C,BFP,INA,IR were higher in Korean T2DM with macroangiopathy patients than Korean controls(p<0.05),However the level of HDL-C was lower in Korean T2DM with macroangiopathy patients than Korean controls(P<0.05).In case-control study in Han nationality showed that the level of WHR,BMI,FPG,TC,TG,LDL-C,BFP,IR were higher in T2DM patients and T2DM with macroangiopathy than controls(p<0.05),and we also found the level of SCr was lower in T2DM patients than T2DM with macroangiopathy(p<0.05).6.The level of SCr was higher in CC genotype group(p<0.05)and the genetic model was complete dominant heredity.The level of FPG was higher in CC genotype group(p<0.05)and the genetic model was complete recessive heredity.In controls,the level of BMI and LDL-C was higher in CC genotype group than AA and AC genotype group(p<0.01).In T2DM with macroangiopathy patents,the level of SCr was higher in CC and AC genotype group than AA group(P<0.05).7.There were no difference in genotype frequency and allele frequency of 2 SNPs above between Han and Korean nationalities in Yanbian from China(p<0.05).However,C allele frequency and CC genotype frequency for rs255758 were lower in Han and Korean nationalities than CEU and YRI(p<0.01).We also found G allele frequency and GG genotype frequency for rs4311394 were higher in Han and Korean nationalities than CEU,African American(P<0.01).Conclusions:1.A novel variant in the ARL15 gene was associated with higher circulating level of SCr(rs255758-C).This same risk allele at ARL15 was also associated with a higher risk of T2DM and macroangiopathy,Which may influence lipid metabolism disorder and impact upon T2DM and macroangiopathy risk.2.The polymorphisms of rs255758 of ARL15 gene were not associated with the protein expression of ARL15.3.There were racial difference for rs255758 and rs4311394 of ARL15 gene. |
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