Study On Association Of The Forkhead Box C2 Gene Polymorphism And Free Fatty Acids With Metoblic Syndrome

Objective: The aim of this study is to disclose the putative promoter region ofFOXC2 genotype,alleles distribution features in people of northern China Hannationality and the association of forkhead box C2 gene polymorphism and free fattyacids(FFA) with metoblic syndrome(MS), and from view of genetic gene and adiposefactor, we want to explore the pathogenesy of MS.Subjects and methods: 510 subjects with no consanguinity selected from Hannationality in Tianjin district and diagnosed MS according to IDF MS diagnosticcriteria. All subjects were evaluated with a 75-g oral glucose tolerance test (OGTT),and fasting plasma FFA was measured.Comparison of levels of plasma FFA wasdone between groups, and genomic DNA was extracted from anticoagulant wholeblood. By means of polymerase chain reaction-restriction fragment lengthpolymorphism (PCR-RFLP) method, the genotypes of the common -512C＞Tpolymorphism in FOXC2 gene were determined. And correlation analyse were alsodone beween genetype, plasma FFA and other characteristic parameter of MS.Results:1. The relationship between plasma FFA level and MS(1) The prevalence of MS,hypertension,diabetes, hypertriglyceridemia,obesity andhyperuricacidemia increased with FFA level. The FFA level was associated with themorbidity rate of MS. (2) FFA correlated positively with most of the glucolipidmetabolism parameter in the correlation analysis(P＜0.05), especially significantlywith TG level, even after adjustment for age, sex, BMI, HOMA-IR using a partialcorrelation. (3) Multiple regression analysis showed that TG and waist line were themain independent factors influencing plasma FFA concentration. 2. The prevalence of the FOXC2-512C＞T alleles and genotypes(1) The prevalence of the FOXC2-512C＞T alleles and genotypes in each groupagreed with Hardy-Weinberg equilibrium law. Similiar to the two Asian countriesJapen and Indian, the frequency of allele C of Chinese was more than allele T(67.2％vs 32.8％), which was different with that in the other Ethnic population.(2) Thegenotype frequency of-512C＞T polymorphism of the FOXC2 gene in group MS+was34.7％for CC, 43.0％for CT, and 22.3％for TT. It was respectively 48.2％,38.4％, and 13.4％in group MS-. There were significant differences in genotype andallele frequencies of -512C＞T polymorphism among the twogroups (P＜0.01), amongwhich group MS- seemed to have higher frequencies of allele T and CT/TT genotypethan that in group MS+(P＜0.01). But there were no difference of the genotypefrequency between group coronary artery disease, hypertension, obesity, diabetes andcontrol groups (P＞0.05). (3) Compared to CC genotype, the carriers of alleleT(CT+TT) group had lower DBP, TG, UA, FFA and 2hIN (P＜0.05), and allele Tgroup had significant lower HOMA-IR than allele C group (3.79±3.71 vs 4.32±4.39P＜0.05). After adjustment for TG level, the difference of UA, FFA betweendifferent genotypes group decreased. In DM, HTG, MS, there were still differencesof TG, DBP, UA and 2h IN between different genotype groups(P＜0.05), but therewas no difference of FFA(P＞0.05). (4) In DM group, genotype TT had lower FFAand FIN than genotype CC and CT groups. In DM female, the carders of alleleT(CT+Tr) group had significant decreased waistline and DBP compared with CCgenotype (P＜0.01), and TT genotype had decreased FFA and FIN compared with theother genotype (P＜0.05). In non DM female had decreased waistline and WHR inTT genotype compared with the carders of allele C (P＜0.05). (5) The genotypefrequency of C＞T polymorphism of the FOXC2-512 gene in group MS-was 34.7％for CC, 43.0％for CT, and 22.3％for TT. It was 42.3％, 39.7％, and 17.9％respectively in NTG·MS+; and50.57％, 37.9％, and11.6％in HTG·MS+. The statistics showed that there was significant difference of the genotype frequency among threegroups (P＜0.01). (6) Compared with the normal metabolism, 1-2 abnomalmetabolisam subjects and MS, the result was the more abnormal metabolismparameter, the higher frequency of allele C and genotype CC, and the lowerfrequency of allele T and genotype TT. (7) Logistic regression analysis showedthat-512C＞T polymorphism of the FOXC2 gene, SBP, DBP, TG, FFA andHOMA-IR were indepengdent variables for MS. And FOXC2-512C＞Tpolymorphism, SBP, TG and HOMA-IR were indepengdent variables for FFA.Conclusion:(1) Compared with the controls, the plasma FFA concentration was elevated inT2DM, obesity, hypertension, hypertriglyceridemia, hyperuricacidemia and MSpatients, and the FFA level was associated with the morbidity rate of MS. (2)Theplasma FFA concentration was negatively correlated with most of parameters ofobesity, glycolipid metabolism, especially significantly with insulin resistance. (3)Visceral obesity and hypertriglyceridemia were single risk factor of high FFAlevel. (4) The allele frequency of of C＞T polymorphism of the FOXC2-512 gene wasdifferent with that of the other ethnic population. (5) Allele C of FOXC2-512C＞Ttended to increase the risk of MS, hypertriglyceridemia and elevation of FFA. But itwas not associated with T2DM and obesity. (6) In the total people, allele T wasassociated with decreased concentration of DBP, TG, UA, FFA, 2hIN andHOMA-IR. In DM female, TT genotype groups had lower waistline, and innondiabetic female had lower waistline and WHR, compared with CC genotypegroups. The results showed allele T of FOXC2-512C＞T was a protective factor ofMS.