| Objectives Epidemiologic studies have shown that serum level of both MIF and PPARγare implicated in several physiologic pathways such as hypertension,lipid metabolism,severity of insulin resistance, inflammatory reaction,and atherosclerosis,all of which are closely related to the pathogenesis of stroke.MIF and PPARγgene exhibit genetically determined structural polymorphisms.Until now,several polymerphisms, i.e.-173G/C,+254(T/C)and +656(C/G)for MIF,Pro12Ala and C1431T for PPARγ,respectively,have been identified.The aim of the present study was to investigate possible effects of MIF-173G/C and PPARγC1431T polymorphisms as well as the interaction between the two tested polymorphisms on the presence of stroke,hypertension,and serum lipid levels in Chinese Han population of Hunan area.Methods A total of 203 healthy individuals,298 patients with with cerebral infarction(CI)and 162 patients with primary cerebral hemorrhage(CH)of Chinese origin were were recruited in this study.The genotypes for the two tested SNPs were detected by polymerase chain reaction-restrictive fragment length polymorphism(PCR—RFLP)and DNA sequence.Serum lipid concentrations were determined by enzymatic analytical chemistry.Results (1)-173G/C of MIF and C1431T of PPARγpolymorphisms exist in Chinese people of Hunan area,with the allele frequencies 0.793/0.207for—173G/C and 0.798/0.202 for 1431 C/T,respectively.No significant differences were observed in genotypes and allele frequencies between stroke patients and controls for MIF-173G/C polymorphism(P＞0.05).As to PPARγC1431T polymorphism,significant higher frequencies of T allele and T/X genotype were confirmed in stroke patients with respect to the control subjects(P＜0.05),especially in patients with hypertention and diabetes mellitus.(2)The MIF-173C allele carriers in CI patients have significant higher level of BMI than-173GG homozygosis(P＜0.05).Compared to the PPARγ1431CC homozygosis,T allele carriers in CI patients have significant higher levels of FBS and LDL-c while low level of HDL-c; T allele carriers in CH subjects only have significantly higher level of TG(P＜0.05).(3)The combined effects of these two genes on stroke risk were examined by subgroup analyses.The result indicated that there exhibited no significant difference between MIF-173 C and non-173C carriers in the incidence of stroke within the PPARγ1431CC genotype subgroup, but the difference appeared within the 1431T/X genotype subgroup, that is to say MIF-173 C allele carriers had a higher risk of stroke than the non-173C carriers(P＜0.05).The combination mutations of PPARγ1431 C-＞T and MIF -173G-＞C have the highest risk of hypertention in CI group(P＜0.05).The MIF -173C carriers in CH patients had a higher incidence of hypertention than the non-173Ccarriers within the PPARγCC genotype subgroup(P＜0.05),however,no similar results was found in the T/X genotype subgroup.As far as diabetes mellitus was concerned,the MIF-173 C allele carriers had higher morbility than the non-173C carriers(P＜0.05),regardless of the PPARγC1431 T variant.(4)In CI patients,the MIF -173C carriers had a significant lower level of LDL-c than the non-173Ccarriers within the PPARγ1431CC genotype subgroup,while the difference was magnified in the PPARγ1431 T/X subgroup,significant higher level of LDL-c,DBPand BMI was observed in -173 C carriers compared to non-173C carriers (P＜0.05).PPARγ1431T / MIF-173 C carriers in CH patients have significant higher level of BMI than 1431T/non-173C carriers.Conclusions(1)No definite conclusion could be reached regarding the involvement of the -173G/C polymorphism of MIF in stroke,whereas PPARγC 1431T polymorphism might contribute to an increased risk of stroke among Chinese Han population of Hunan area.(2)The MIF -173C allele might have a significant correlation to higher BMI levels in CI patients.The C1431T.polymorphism of PPARγmight be implicated in the lipid pathways and glyco-metabolism. (3)PPARγC1431T and MIF-173G/C polymorphisms have a possible interaction in their effects on the presence of serum lipid concentrations,blood pressure and BMI.The association of MIF -173G/C genotype to them seems to be magnified to the synergistic effect of PPARγ1431C-＞T variant,which may result in a possible effect on stroke risk.
|
PDF Full Text Request