Research On The Peak Bone Mineral Density In Han And Uyghur Female:to Combine The Environmental Factors And Different Genes

Objective: To determine bone mineral density (BMD) of Uygur and Han nationalityof females in health people in Xinjiang area, to investigate the status of BMD and thechange regularities of BMD with age. To establish BMD reference data based on lumbarvertebra of quantitative CT (QCT) in Uygur and Han.This paper discuss the influentialfactors for the peak of the bone mineral density, such as the genetic factors andenvironmental factors.the study is combining and using the multiple regression analysisand multifactor di-mensionality reduction methods to analyze the relationship betweenthe environmental factors and candidate gene polymorphisms, including the interactionbetween these two factors which may affect the peak bone mineral density in Han andUyghur female. To reveal the differences in the gene level which influence on peak bonemineral density in the Han and Uyghur female in Xinjiang region, from the newperspective to explore the mechanism of primary osteoporosis.Methods:(1) A retrospective analysis of a total of1244women (Han and Uygurnationality) at the physical health medical center in the First Affiliated Hospital ofXinjiang Medical University who aged17-87years old had been underwent QCT oflumbar vertebra for BMD by16-slice spiral CT and QCT3000System. BMD of lumbarvertebra with age-related changes was fitted in the whole healthy women population by8kinds of regression models. Best model equations of fitting were found for the Han andUygur female. The mean BMD values were expressed as mean and standard deviation(SD) according to different nationality and age, which per5years be in one group.Comparisons of two groups were calculated through t-tests.(2) The BsmI (rs1544410)、CDX2(rs11568820), TaqI (rs731236), Tru9I (rs757343) single nucleotide polymorphism (SNP) of the VDR gene, the rs3751143、rs1653624、rs28360457SNP ofthe P2X7R2gene, the rs1298989SNP of the CATSPERB gene and the rs3762397SNPof the NR5A2gene were genotyped by PCR-RFLP using SNaPshot.The study groupconsisted of305Han and216Uyghur subjects which is unrelated healthy women aged20-40years. The BMD of the lumbar spine was measured using quantitative computedtomography (QCT). Physical activity and life styles were assessed by aquestionnaire.Based on the one way ANOVA to analyze of distribution of the genotypeand allele frequencies in the candidate genes, comparison of the Han and Uygur female.To analyze the relationship between the polymorphisms of candidate genes and bonemineral density in two nationalities.LD and haplotypes construction were analyzed forSNPs of VDR and P2X7R2genes.(3) To analyzed the environmental factors that affectthe peak bone density in the Han, Uygur such as the diet, physical activity, reproductivelactation, menstruation, occupation.(4) multiple regression analysis and multifactordi-mensionality reduction methods to analyze the relationship between the environmentalfactors and candidate gene polymorphisms, including the interaction between these twofactors which may affect the peak bone mineral density in Han and Uyghur female.Results:1) The peak bone mass of the lumbar spine occurred before the age35bothHan and Uyghur, the age of Uighur women was earlier than the Han, and after reachingpeak bone mass there was a short decreased trend in the curve, then slow steady declinein the next age interval. The BMD showed a sharp decline after50years both Uygur andHan nationality females, in particular, the Uygur females of＞65years. OP prevalencerates increased with age, the two nationality was similar in the＜50year group,prevalence of Uighur female was higher than the Han in≥50age group.A cubicregression model was better fitted with age related changes as compared to the otherregression models, and the coefficients of determination (R2) of fitting curve were0.593-0.626(P＜0.001).2) Hardy-Weinberg Equilbrium was evident for candidate genepolymorphism in the Uygurs and Hans. There was difference in genotypes and allelesdistribution of candidate gene between these two nationalities females.(1) A significantassociation difference between peak bone mineral density and rs1544410polymorphismof VDR gene was found in both Uygurs and the Hans.The BMD values in Uygur subjectswith the Bb genotype were significantly (P＜0.05) higher than in those with the BBgenotype, the BMD values in Han subjects with the bb genotype were significantly (P＜0.05) higher than in those with the Bb genotype.No significant association differencebetween PBMD and rs11568820, rs731236, rs757343polymorphism of VDR gene was found.(2) A significant association difference between peak bone mineral density andrs28360457polymorphism of P2X7R2gene was found in Han, the BMD values with theGG genotype were significantly (P＜0.05) higher than in those with the othersgenotype.A significant association difference between peak bone mineral density andrs3751143polymorphism of P2X7R2gene was found in Uyghur, a high BMD wasassociated with the CC genotype.(3) A significant association difference between peakbone mineral density and rs3762397polymorphism of NR5A2gene was found in bothHan and Uyghur female, the BMD values in Uygur subjects with the CC/TT genotypewere significantly (P＜0.05) higher than in those with the CT genotype, the BMD valuesin Han subjects with the TT/CT genotype were significantly (P＜0.05) higher than inthose with the CC genotype.(4) No significant association difference between PBMDand rs1298989polymorphism of CATSPERB gene was found in Han. A significantassociation difference between peak bone mineral density and rs1298989polymorphismof CATSPERB gene was found in Uyghur female, the BMD values in Uyghur subjectswith the GA genotype were significantly (P＜0.05) higher than in those with the GGgenotype.(5) Apply the multifactor di-mensionality reduction methods to analyze theinteraction among the9single nucleotide polymorphism of4candidate gene, aninteraction model to selecting4locus on genes that is established as the best gene-geneinteraction model, This model including BsmI (rs1544410), CDX2(rs11568820), TaqI(rs731236), rs3762397that is characterized with the high prediction accuracy(TA=0.8862) and the best cross-validation consistency (CVC=10/10).3) Non-geneticenvironmental factors for peak bone mass were evaluated, such as body type, exercise,brain manual (occupation), drinking habits, drinking tea habit, fruit habit, blues habits,drinking yogurt habits, age at menarche, age of first birth, fertility, lactation history.(1)Bone mineral density with normal body in Han was lower than the same body in Uygur,No significant association difference between the bone mineral density with underweightbody、overweight body、fat body in the Han and Uighur.(2) The BMD values withhabitual regular milk consumption were significantly (P＜0.05) higher than in those withthe irregular milk consumption in both Han and Uygur subjects.The BMD values werehigh who with habitual regular milk or yogurt consumption, the BMD values withhabitual regular yogurt consumption were significantly (P＜0.05) higher than in thosewith the irregular yogurt or not consumption in Uygur subjects. Also the BMD valueswith habitual regular yogurt consumption in Uygur were significantly (P＜0.05) higherthan Han subjects.the BMD values with habitual tea milk consumption in Han were significantly (P＜0.05) higher than Uygur subjects.(3) No differences were observed inthe BMD values with different occupation for Han subjects, a high BMD was associatedwith the workers or other professionals in Uyghur subjects, a lower BMD was associatedwith the junior high school education or less in Uyghur subjects.(4) A significantdifferences were observed in the BMD values with different degree of physical activityfor both Han and Uyghur subjects, the BMD values with the group of severe physicalactivity were significantly (P＜0.05) higher than in those with group of mild physicalactivity. No differences were observed in the BMD values with the same degree ofphysical activity for Han and Uyghur subjects.(4) The menstrual cycle of Uyghur femalewas longer than that of Han, an average of29.21days, the Initial childbearing age wasearlier than that of Han for about1.36years.No differences were observed in the BMDvalues for menarche age、menstrual menstruation in both Han and Uyghur subjects.Nodifferences were observed in the BMD values with feeding time less than6months ormore than6months for Han subjects, the BMD values with feeding time less than6months were significantly (P＜0.05) higher than in those with the more than or equal6months for Uyghur. No differences were observed in the BMD values with the samedegree of feeding time for Han and Uyghur subjects (P＞0.05).(6) Multiple regressionanalysis showed that the factors for the peak bone mass in Han included habitual milkconsumption、physical activity、habitual fruit consumption、mental or manual. Thegreatest impact on BMD was observed for habitual milk consumption. Also Multipleregression analysis showed that the factors for the peak bone mass in Uygur includedhabitual tea consumption、habitual milk tea consumption、habitual fruit consumption、habitual milk consumption. The greatest impact on BMD was observed for habitual milktea consumption.4) Combined with environmental and genetic factors, multipleregression analysis showed that the factors for the peak bone mass in Han includedhabitual milk consumption、physical activity、habitual fruit consumption、habitual yogurtconsumption、rs757343、rs3762397、rs28360457.Also the analysis showed that the factorsfor the peak bone mass in Uygur included habitual tea consumption、habitual milk teaconsumption、 habitual milk consumption、 menstrual menstruation、 rs3762397、rs1298989、rs3751143.The locus rs757343and physical activity have an interactionrelationship, The locus rs3762397and habitual yogurt consumption have an interactionrelationship in Han; The locus rs1298989and habitual milk consumption have aninteraction relationship in Uygur.Conclusion:1) This study establishes the BMD of QCT reference databases of lumbar vertebra in Uygur and Han females in Xinjiang area, which suggested that BMDof female adults changed along with increasing age, with the sTableBMD in the age of20to40years, and sharp decline after50years old, in particular, Uygur females may beeasier to suffer from the OP than Han females.2) The differences observed in thegenotype and allele frequencies distributions of9locus on genes between Han andUyghur, it may be the result of the existence of racial differences. The attainment andmaintenance of peak bone mass at lumbar vertebra had associated with the rs1544410inthe VDR gene、the rs3762397polymorphism in the NR5A2gene in both Han andUyghur.the attainment and maintenance of PBMD had associated with the rs28360457polymorphism in the P2X7R2gene in Han, and the association with the rs3751143polymorphism in the P2X7R2gene and rs1298989polymorphism in the CATSPERBgene in Uyghur.The rs11568820、rs731236、rs757343、rs1653624polymorphism seemnot potentially influence on peak bone mass in Uyghur and Hans women.There were thesame environmental factors effect on PBMD, also there are different for Uyghur andHans women.Habitual fruit consumption and habitual milk consumption were the mainprotective predictors of increased PBMD in the lumbar spine, physical activity andoccupation may play a role in PBMD. In particular, Diet and living habits Significanteffect on PBMD of Uygur women.4) Combined with environmental and genetic factors,the result of multiple regression analysis showed that environmental and genetic factorsplay a role in the PBMD of Hans and Uygur that maintained PBMD. There was aninteraction between the part of polymorphic loci and environmental factors, that mayplay interaction effect on PBMD.