The Associations Of L162V And C2528G Polymorphism Of The PPAR Alpha Gene With Early-onset Type 2 Diabetes Mellitus

Background:Type 2 diabetes mellitus is increasing with the social lifestyle changes and increasing obesity. In recent years, the age of onset of T2DM is falling. Most foreign academics agreed that the early-onset T2DM means the adult diagnosed at≤40 years of age. The early-onset T2DM has much more obvious tendency of familial aggregation, poor blood glucose control, severe dyslipidemia, compared with late-onset T2DM, early-onset T2DM need insulin therapy earlier. Severe insulin resistance andβ-cell failure are pathophysiological processes of early-onset T2DM. Studies have shown that dyslipidemia is the early performance of insulin resistance. Recent studies have shown that peroxisome proliferator-activated receptor alpha(PPARa) widely expressed in the tissue of vigorous fatty acid me-tabolism. PPARa regulates the transcription of key proteins involved in lipid metabolism, immunity reaction, cell differentiation, as well as inflam-matory reactions. Previous studies have found that dyslipidemia of T2DM has association with the PPAR a L162V and C2528G polymorphism.Objective:The purpose of this study is to explore the differencese of blood glucose control, serum lipids andβ-cell function between early-onset T2DM and late-onset T2DM. To explore the correlations of PPARaL162V and G2528G polyphism to early-onset T2DM.Methods:A total of 393(181 men and 202 women) T2DM subjects were recruited and divided into two groups:early-onset and late-onset groups which were defined as diagnosed at≤40 and> 40 years of age, respectively. Early-onset T2DM subjects 103(63 men and 40 women), whose average age is 36.33±4.02 years. Late-onset T2DM subjects 290(118 men and 172 women), whose average age is 56.36±9.56 years. Extracted peripheral blood white blood cell genomic DNA to detect PPARaL162V and G2528 polymorphism by the application of polymerase chain reaction(PCR) and calculate gene type and allele frequency of each group as well as clinical biochemical indicators.Results:1. The fasting plasma glucose(FPG), triglyceride (TG), uric acid (UA) are higher in early-onset T2DM group than in late-onset T2DM group.2. The overall frequencies of LL,LV,VV in early-onset T2DM group and in late-onset T2DM group were 93.2%,0%,6.8%, and 97.6%,0%, and 2.4%respectively. The L162 allele frequency is 93.2%, and V162 allele frequency is 6.8%in early-onset T2DM group, and the LI62 allele frequency is 97.6%, and VI62 allele frequency is 2.4%in late-onset T2DM group. There was statistical difference in the gene type frequency distri-bution between the two groups by check-up.3. The overall frequencies of GG, GC, CC in early-onset T2DM group and in late-onset T2DM group were 89.3%,6.8%,3.9%, and 94.8%,4.5%, and 0.7%respectively. The G2528 allele frequency is 92.7%, and C2528 allele frequency is 7.3%in early-onset T2DM group, and the G2528 allele frequency is 97.1%, and C2528 allele frequency is 2.9%in late-onset T2DM group. There was statistical difference in the gene type frequency distri-bution between the two groups by check-up.4. In early-onset T2DM group V162 allele has higher FPG,2hPG, and total cholesterol (TC) than L162 allele. In late-onset T2DM group V162 allele has higher FPG and TG, lower,β-cell function than L162 allele.5. In early-onset T2DM group C2528 allele has higher glycosylated hemoglobin (HbA1C),2hPG, TC, TG, apolipoproteinB(APOB) than G2528 allele. In late-onset T2DM group C2528 allele has higher TC, low density lipoprotein cholesterol (LDL-C), Apoa apolipoprotein(APOA1) than G2528 allele.Conclusion:1. The early-onset T2DM group has poor blood glucose control, more severe dyslipidemia and higher uric acid when compared with late-onset T2DM group.2. In the early-onset T2DM group PPARaV162 and C2528 alleles frequencies are more elevatory than the late-onset T2DM group.3. In the early-onset T2DM group and late-onset T2DM group, V162 allele has higher blood glucose, more severe dyslipidemia andβ-cell failure when compared with L162 allele.4. In the early-onset T2DM group and late-onset T2DM group, C2528 allele has poor blood glucose control and more severe dyslipidemia.5. PPARaL162 and G2528G polyphism may have associations to early-onset T2DM.