| Objective: OCTs and MATEs played a part in the processes of metformin transport in human boby. We selected five single nucleotide polymorphism(SNP) sites rs628031, rs683369, rs316019, rs2048327 and rs2252281 which could affect the function of these two transporters or which had a high frequency of minor allele. Genotype of SNP sites above-mentioned of 130 type 2 diabetes mellitus(T2DM) patients who were treated with metformin at the first time was assayed. Then analyze the relationship between SNP and the gastrointestinal side effects as well as the efficacy of metformin.Methods:1 Genotype assaying: collect blood samples from 130 T2 DM patients who received metformin at the first time, analyze the five sites rs628031, rs683369, rs316019, rs2048327 and rs2252281 by allele-specific polymerase chain reaction(AS-PCR) and gel electrophoresis methods.2 General data collection: including the general clinical data and related biochemical indicators.3 Follow up visit: after three months, counsel the participants to identify whether they had any symptoms indicated gastrointestinal side effects, explore the relationship between the genetic polymorphisms of the five gene sites and gastrointestinal side effects. Then again test FPG, PPG, Hb A1 c of the patients who took metformin as a monotherapy three months after enrollment.Results:1 Compared with gastrointestinal tolerance group, there was no statistically significant difference in the sex composition, diabetic duration, body mass index(BMI), diastolic blood pressre(DBP), usage of insulin(P>0.05) in the gastrointestinal intolerance group. But patients in intolerance group were older and their systolic blood pressure(SBP) were higher than the tolerance group(P<0.05);2 Compared with gastrointestinal tolerance group, there was no statistically significant difference in the Hb A1 c, FPG, PPG, high-density lipoprotein(HDL-C), low-density lipoprotein(LDL-C), totle cholesterol(TC), serum creatinine(Scr), urea nitrogen(UN) and uric acid(UA) in the gastrointestinal intolerance group(P>0.05). But the triglyceride(TG) level of gastrointestinal intolerance group was lower than gastrointestinal tolerance group(P<0.05);3 The distributions of five SNP sites genotype were accorded with the Hardy-Weinberg equilibrium among all 130 participants. The genotype of AA, AG, GG were detected in rs628031. After considering some factors such as age, sex, course of diabetes, SBP, TG, metformin doses etc, the genotype distribution and allele frequency of the two groups showed statistical significance, the frequency of rs628031 A allele in intolerance group was higher than tolerance group(P<0.05). Three genotypes of GG, GC, CC were detected in rs683369. The genotype distribution and allele frequency of the two groups showed no statistical significance(P>0.05). Three genotypes of GG, GT, TT were detected in rs316019. The genotype distribution and allele frequency of the two groups showed no statistical significance(P>0.05). Two genotypes of AA, AG were detected in rs2048327. GG Genotype failed to be checked out. The genotype distribution and allele frequency of the two groups showed no statistical significance(P>0.05). Three genotypes of TT, TC, CC were detected in rs2252281. The genotype distribution and allele frequency of the two groups showed no statistical significance(P>0.05);4 Among 43 T2 DM patients who taken metformin as a monotherapy for three months, we found that after considering some factors such as age, sex, course of diabetes, BMI, metformin doses etc, ones with GG genotype of rs628031 exhibited greater reduction in their FPG level than those with the AA, AG genotypes(P<0.05). The differences of the reductions in PPG, Hb A1 c levels between AA, AG, GG genotypes cases had no statistical significance(P>0.05). There was no statistical significance of the reductions in their FPG, PPG, Hb A1 c level between rs683369 GC and CC genotypes(P>0.05). There was no statistical significance of the reductions in their FPG, PPG, Hb A1 C level between rs316019 GG, GT genotypes(P>0.05). There was no statistical significance of the reductions in their FPG, PPG, Hb A1 c level between rs2048327 AA, AG genotypes(P>0.05). There was no statistical significance of the reductions in their FPG, PPG, Hb A1 c level between rs2252281 TT, TC, CC genotypes(P>0.05).Conclusions:1 There was no relationship between sex, course of diabetes, BMI, DBP, usage of insulin and the presence of gastrointestinal side effect of metformin. Age and SBP were related to gastrointestinal side effect of metformin.2 There was no relationship between Hb A1 c, FPG, PPG, HDL-C, LDL-C, TC, Scr, UN, UA and gastrointestinal side effect of metformin. TG was related to gastrointestinal side effect of metformin.3 Relationship between the A allele of the rs628031 in OCT1 and the presence of the gastrointestinal side effect of metformin was found. No relationship was found between the polymorphisms of OCT1 rs683369, OCT2 rs316019, OCT3 rs2048327, MATE1 rs2252281 and the presence of the gastrointestinal side effect of metformin.4 The polymorphisms of OCT1 rs628031 may affected the efficacy of metformin for reducing FPG. The polymorphisms of OCT1 rs683369, OCT2 rs316019, OCT3 rs2048327, MATE1 rs2252281 were not associated with hypoglycemic effect of metformin... |
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