| Part I Prevalence and its risk factors of familial type2diabetes mellitus with DR[Objective](1) To detect the prevalence and the genetic pattern of familial type2diabetes mellitus with DR.(2) To analyze the risk factors of familial type2diabetes mellitus with DR of the population.[Methods] Recorded the clinical data from all subjects in questionnaires and laboratory test of the biochemical indexes were made. ELISA was used for true insulin,proinsulin and25(OH) D3levels. Fok I,Bsm I,Apa I and Taq I genotypes of vitamin D receptor (VDR) gene were detected by PCR-RFLP. Statistical analysis was made.【Results】(1) In19families of147folks, two cases were of newly diagnosed T2DM with DR (2/147) and the prevalence of DR in the population was22.45%. The prevalence of DR in probands,first-degree relatives and second-degree relatives were respectively57.89%,22.11%,3.03%. It was higher in women (17.69%) than in men (4.76%). The prevalence in mothers of probands with DR was very high (83.33%), and there was no statistical significance between brothers and sisters in siblings with DR (22.22%vs20%, P=0.879).(2) Probands,first-degree relatives and second-degree relatives were respectively (52.58±10.27),(47.65±17.17),(21.94±14.32) years old. The T2DM pronds with DR group and the T2DM siblings with DR group were respectively (58.09±7.71) and (56.09±3.99) years old; there was no statistically significance between two groups (P>0.05).(3) The number of families with≥2DR patients accounted for47.4%. The number of families with mothers of DR as probands was10.(4) In different plasma glucose levels and different kinship levels of the population, Fok I,Bsm I,Apa I and Taq I genotypes and frequencices of all alleles of the VDR gene were not statistically significant (P>0.05).(5) Compared to the T2DM probands without DR, age(P<0.01), duration of diabetes,FCP and PCP (P<0.05) in the T2DM probands with DR were statistically significant. Using binary logistic regression analysis, it suggested that age and duration of diabetes were both risk factors for probands with DR.(6) Compared to the T2DM siblings without DR, HbAlc,Ca2+and PCP (P<0.05)in the T2DM siblings with DR were statistically significant. Using binary logistic regression analysis, it suggested that Ca2+was the only independent protective factor for the T2DM siblings with DR.【Conclusion】(1) The incidence of newly diagnosed T2DM with DR was1.36%and the prevalence of DR was22.45%. It was higher in women than in men. The prevalence in mothers of probands with DR was high, and there was no differences between brothers and sisters in siblings with DR.(2) The further the kinship of the population was, the lower prevalence of DR was. Compared to the T2DM probands with DR, the T2DM siblings with DR was in advance.(3) DR maybe happen in a familial aggregation way, and maternal inheritance is an important feature of the study population.(4) There were no differences in the three genotypes and allele frequencies of Fok I,Bsm I,Apa I and Taq I of the VDR gene between the T2DM probands with DR and the T2DM siblings with DR.(5) It suggested that age and duration of diabetes were both risk factors for the T2DM probands with DR and Ca2+was the only independent protective factor for the T2DM siblings with DR in the population. Part II Assosiation study of vitamin D receptor gene polymorphisms and familial type2diabetes mellitus with DR【Objective】(1) To explore serum25(OH)D3levels and vitamin D deficiency in the familial T2DM with DR.(2) To analyze the polymorphisms of Fok I, Bsm I, Apa I and Taq I of the VDR gene in the population and investigate the association of4loci and familial T2DM with DR.【Methods】 Recorded the clinical data from all subjects of DR1, DR0, T2DM, NC and R group in questionnaires. Laboratory test of the biochemical indexes were made, and ELISA was used for25(OH) D3levels. Fok I,Bsm I,Apa I and Taq I genotypes of vitamin D receptor (VDR) gene were detected by PCR-RFLP. Statistical analysis were made.【Results】(1) The value of age,duration of diabetes, FPG, PPG and HOMA-IR was maximum while ISI was the minimum in DR1group.(2) Frequency of FF, Ff and ff genotypes in DR1group was respectively25.1%,54.1%and20.8%; and there was no statistically significance of three genotyps in the five groups (P>0.05). The frequency of Ff genotype was minimum in DR1group, and the frequency of FF genotype in familial T2DM patients (25.1%～26.6%) was higher than in T2DM patients without family history (22.2%). The frequency of F and f allele was respectively52.2%and47.8%in DR1group, and there was no statistically significance of two alleles in the five groups (P>0.05).(3) Frequency of BB, Bb and bb genotypes in DR1group was respectively0.5%,7.2%and92.3%; there was no statistically significance of three genotyps in the five groups (P>0.05). It was maily for bb genotype in5groups of the population; the frequency of bb,BB genotype was respectively maximum (92.3%) and minimum(0.5%) in DR1group, and the frequency of bb genotype in DR1group was much higher than in DRo group (86.0%); the frequency of bb genotype in familial T2DM patients (86.0%～92.3%) was much higher than in T2DM patients without family history (78.9%), as well as normal control group (85.9%). The frequency of B and b allele was respectively4.1%(minimum)and95.9%(minimax)in DR1group, and there was statistically significance of two alleles in the five groups (P<0.05). After further pairwise comparisons, it was found that there was statistically significance of two alleles between NC group and DR1group, DR1group and R group (P<0.05). The frequency of b allele in familial T2DM patients (92.4%～95.9%) and in familial DR patients (95.9%) were both higher than in T2DM patients without family history (88.9%), NC group and R group.(4) Comapared its3genetypes of4loci of VDR gene between DR1group in this study and DR group in our last study, it was found that there was statistically significance of3genetypes of Fok I between2groups (P<0.05). Comapared its3genetypes of4loci of VDR gene between DR1group in this study and DR group in our last study, it was found that there was statistically significance of3genetypes of Fok I between2groups (P<0.05).Comapared its3genetypes of4loci of VDR gene between DR0group,T2DM group in this study and NDR group in our last study, it was found that there was statistically significance of3genetypes of Fok I and Bsm I among3groups (P<0.01). After further pairwise comparisons, it was found that there was statistically significance of3genotypes of Fok I between NDR group and DR0group (P<0.01), NDR group and T2DM group (P<0.05), and there was statistically significance of3genotypes of Bsm I between NDR group and T2DM group (P<0.01).(5) Frequency of AA, Aa and aa genotypes in DR1group was respectively4.9%,40.4%and54.7%, and frequency of A and a allele was respectively25.1%and74.9%in DR1group. There was no statistically significance of three genotyps and two alleles in the five groups (P>0.05).(6) Frequency of TT and Tt genotypes in DR1group was respectively94.0%,6.0%, and frequency of T and t allele was respectively97.0%and3.0%in DR1group. There was no statistically significance of three genotyps and two alleles in the five groups (P>0.05).(7) In DR1and DRo groups, the allelic association degree of alleles of BsmI, Apal and TaqI (D'value) was>0.7, and there was no significant difference in the frequency of3haplotypes of BAT, bAT and baT between the two groups (P>0.05).(8) According to the common standard and the referenced standard, vitamin D deficiency/insufficient accounted for up to85%in all of the5groups and the ratio between the5groups of in each standard was statistically significant (P<0.01). Further pairwise comparisons, it was found that there was statistically significance between NC group and T2DM group (P<0.05), NC group and R group (P<0.01), DR, group and R group (P<0.01).(9) In DR1, DR0and T2DM group,25(OH) D3was negatively associated with WHR, TG, FCP and PCP, and positively associated with HDL-C(P<0.05); after multiple linear regression analysis it showed that the only variable WHR entered the model. In DR1group,25(OH)D3was positively associated with duration of diabetes, TC, HDL-C and LDL-C (P<0.01); after multiple linear regression analysis it showed that the only variable HDL-C entered the model.(10) Taking the occurrence of DR as the dependent variable, after binary logistic regression analysis, it showed that the family history of diabetes, duration of diabetes, FPG and HOMA-βentered the model equation.【Conclusion】(1) Family history of diabetes may affect genotypes of Fok I and Bsm I in T2DM and DR patients, especially in familial T2DM and DR patients. It suggested Fok I and Bsm I geneotypes of VDR gene may play a role in the development of T2DM and DR, while Apa I and Taq I geneotypes of VDR gene had nothing to do with T2DM and DR.(2) There is a significant linkage disequilibrium among Bsm I, Apa I and Taq I of VDR gene in familial DR population.(3) Vitamin D deficiency/insufficient existed widely in the whole population, and familial DR population accounted for more than90%.(5)25(OH)D3levels showed a linear positive correlation with HDL-C in familial DR patients.(6) Family history of diabetes, duration of diabetes, FPG and HOMA-βis an independent risk factor of the familial DR patients. |
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