The Interrelation Of Heme Oxygenase-1 Gene Polymorphism And Lower Extremity Vascular Disease In Diabetic Patients

Objective:To investigate the related risk factors of lower extremity vascular disease in T2DM patients. To investigate the interrelation of heme oxygenase-1 gene promotor region (GT) dinucleotide repeats polymorphism and the inherit susceptivity of Lower extremity vascular disease in T2DM patients.Methods:A case-control study was used. Subjects involved 98 healthy controls,96 T2DM patients and 98 T2DM patients with lower extremity vascular disease(LEVD) in the first affiliated hospital of Shantou University Medical colleage within 2008-12-1—2009-10-1. All of them were unrelated Chinese Han origin. We excluded all subjects with chronic obstructive pulmonary disease, lung cancer, bronchial asthma, coronary heart disease, stroke diseases. We recorded clinical data. Peripheral venous blood was sampled at fasting for detecting FPG, GHbAlc, TC, TG, LDLc, HDLc and extracting genomic DNA. The HO-1 gene was amplified by polymerise chain reaction(PCR) and the (GT)n repeat length polymorphism was assessed by native-polyacrylamide gel electrophoresis (Native-PAGE). All data was analysised by SPSS 13.0 software package.Results:1. No significant difference existed in constituent ratio of sex, age between DM group and NC group(P>0.05). No significant difference existed in constituent ratio of sex, age between LEVD group and NC group(P>0.05). Age, BP, course of disease in LEVD group were significantly higher than those in DM group(P<0.01). BMI, SBP, DBP, FPG, GHbA1c, TC, TG in LEVD group and DM group were significantly higher than those in NC group(P<0.01).2. HDLc in LEVD group and DM group were significantly lower than those in NC group(P <0.01).HDLc in LEVD group were significantly lower than those in DM group(P< 0.01).LDLc in DM group were significantly higher than those in NC group(P<0.05). LDLc in LEVD group were significantly higher than those in DM group(P<0.05)and in NC group(P< 0.01). TG in LEVD group were significantly higher than those in DM group(P<0.01).No significant difference existed in FPG, GHbAlc, TC between LEVD group and DM group(P> 0.05).3. According to the results of ankle brachial index and Doppler ultrasound Test,194 T2DM patients were divided into four groups, without lower limb vascular disease group (DM group), mild group with LEVD, moderate group with LEVD, severe group with LEVD. Analysis of covariance was used to test differentes risk factors in that four groups. Results showed that age, course of disease, HDLc, BP distribution were significant different among groups (P< 0.01);TG distribution were significant different among groups (P<0.05),. The logistic analysis showed that age, course of disease, TG, BP were independent risk factors for the development of peripheral vascular disease in T2DM.4. According to the difference of (GT)n repeats,HO-1 allele was discriminated to three groups: class S less repeats (<25), M(25-29) and class L more repeats (≥30). Leading to SS, SM, SL, ML, MM and LL genotypes. According to whether have S allele,HO-1 genotype was divided into two groups:Ⅰ(SS SM SL),Ⅱ(MM ML SL).The results showed that HO-1 genotype with S allele were more frequently in DM group than in LEVD group(47.9% vs 33.7%χ2=3.6996 P=0.048 OR=1.815) and HO-1 genotype with S allele were more frequently in NC group than in DM group(64.3% vs 47.9%χ2=5.278 P=0.022 OR=1.957).Conclusions1. There was association between Heme oxygenase-1 gene promotor region (GT) dinucleotide repeats Polymorphism and the inherit susceptivity of lower extremity vascular disease in T2DM patients. The longer repetitive sequence may exhibit a increased hereditary susceptibility of peripheral vascular disease.2. There was association between Age, course of disease, BP, TG, LDLc, HDLc and lower extremity vascular disease in T2DM. There was association between Age, course of disease, TG, HDLc, BP and the degree of lower extremity vascular disease in T2DM.3. Age, course of disease, BP were independent risk factors for the development of peripheral vascular disease in T2DM.