Association Between Single Nucleotide Polymorphisms In The PRKAA2 Gene And Type 2 Diabetes Mellitus And Related Metabolism

Objective To study the genotype distribution of 5'-AMP-activated protein kinase alpha-2 subunit gene PRKAA2 rs10889007(301A >T),rs2746338(201A>G) and rs857155(440C>A) polymorphisms in Han people from chongqing,China.To explore the association between the three single nucleotide polymorphisms(SNPs) with type 2 diabetes mellitus(T2DM) and with related clinical and metabolism.Methods (1) In the study, 523 patients with type 2 diabetes (Case group) and 312 normal control subjects (Control group) from Chongqing were enrolled. Three single nucleotide polymorphisms(SNPs) rs10889007(301A>T) in the intron 1 region, rs2746338(201A>G) in the intron 2 region and rs857155(440A>C) in the intron 6 region of PRKAA2 were genotyped in all the subjects enrolled using PCR and restriction fragment length polymorphism (RFLP). Body mass index(BMI),waistline,hip circumference,blood pressure,plasma glucose, serum insulin and lipid profile, high-sensitivity C-reactive protein(hsCRP ) and non-esterified fatty acid(NEFA) were measured. Homeostasis model assessment of insulin resistance (Homa-IR) and disposition index (DI) were used to estimate insulin resistance andβ-cell function respectively. (2) To examine the linkage disequilibrium (LD) structure, pairwise LD and haplotype.Results (1) In PRKAA2 rs10889007(301A>T),the frequencies of AA,AT,TT genotype in case group were 31.0%,52.4%,16.6% respectively, 25.6%,58.3%,16.1% respectively in control group.The distribution rates of genotype were found no statistic difference between case group and control group(P>0.05);the frequencies of minor (T) allele had no significant difference between two groups(42.8%υs 45.2%,P>0.05).(2) In PRKAA2 rs2746338(201A>G), the frequencies of AA,AG,GG genotype in case group were 43.8%,54.4%,10.8% respectively, 39.3%,52.6%,8.1% respectively in control group.The distribution rates of genotype were found no statistic difference between case group and control group(P>0.05);the frequencies of minor (G) allele had no significant difference between two groups(39.1%υs 34.4%,P>0.05).(3) In PRKAA2 rs857155(440C>A), the frequencies of CC,CA,AA genotype in case group were 27.2%,56.7%,16.1% respectively, 22.3%,58.6%,19.2% respectively in control group.The distribution rates of genotype were found no statistic difference between case group and control group(P>0.05);the frequencies of minor (A) allele had no significant difference between two groups(48.5%υs 44.5%,P>0.05).(4) There was no statistic difference among BMI,waist-to-hip ratio(WHR),blood pressure,plasma glucose, serum insulin and lipid profile, high-sensitivity C-reactive protein(hsCRP ) , non-esterified fatty acid(NEFA),HOMA-IR and DI of every genotype in three SNPs of PRKAA2(P>0.05) .(5) Four haplotype frequencies constructed with rs10889007(301A>T) and rs2746338(201A>G) of PRKAA2 gene had no statistic difference between case group and control group(P>0.05).Conclusion There is no association between three SNPs rs10889007(301A>T),rs2746338(201A>G) and rs857155(440C>A)of PRKAA2 gene with T2DM in Chongqing area.