Association Between Obesity And Genetic Polymorphism Of MC4R,SH2B1,NEGR1 In Tibetans

ObjectiveBy analyzing the distribution characteristics of the polymorphism of the gene of the Tibetan obese population and the normal population of Melanocortin-4 Receptor(MC4R)gene,Src homology 2 B adapter protein 1(SH2B1)gene,and Neuronal Growth Regulator 1(NEGR1)gene,the relationship between the polymorphism of the above gene sites and tibetan obesity in Tibet is explored from a genetic point of view.MethodsAccording to the obesity determination criteria of the China Guidelines for the Prevention and Control of Adult Overweight and Obesity,70 people(male 35,female 35)and 70(male and 35 female)were screened for obesity by random sampling among the 1,453 Tibetans who participated in the Tibetan National Health Check-up at the Tama Community Health Service Center in the city of Lhasa.The DNA fragments of the MC4 R gene rs17782313,rs71336392,SH2B1 gene rs7359397 and NEGR1 gene rs3101336 were used,and PCR product identification was carried out by agar gel electrophoresis method.The target gene is sequenced by Sanger sequencing.The relationship between gene sites and obesity was analyzed by statistical methods such as independent sample T-test,single-factor variance analysis,card-side test and Logistic regression analysis.The interaction between genes is analyzed by GMDR software.Results1.MC4 R gene rs17782313 site obesity group genotype distribution frequency TT: 60%,TC: 37.1%,CC: 2.9%;Tibetan male TC genotype carriers’ weight,BMI,fat content,body fat rate,visceral fat content,subcutaneous fat content,torso fat content,torso fat rate,left upper limb fat,left upper limb fat,left lower limb fat rate,right upper limb fat rate,right upper limb fat rate,right lower limb fat content,right lower limb fat rate and other indicators are significantly higher than TT gene carriers(P<0.05).In Tibetan women,in addition to the torso fat rate and right lower limb fat rate of the two indicators,the other indicators C allele carriers are significantly higher than TT genotype carriers(P<0.05),with CC genotype carriers the highest,TC genotype carriers second.Compared with the normal group,there were significant differences in the frequency distribution of MC4 R gene rs17782313 bit genotypes and alleles(P<0.05),and the CC genotype and C alleles had higher rates in the obesity group.2.MC4 R gene rs71336392 site obesity group genotype distribution frequency TTTCT: 60%,TCT(missing hybrid): 37.1%,TCT(pure deficiency):2.9%;Normal group genotype distribution frequency TTTCT: 95.7%,TCT(missing hybrid): 4.3%,TCT(pure missing): 0%,all in line with Hardy-Weinberg’s law,with group representation.Tibetan male TCT hybrid missing individual weight,BMI,fat content,body fat rate,visceral fat content,subcutaneous fat content,torso fat content,torso fat rate,left upper limb fat amount,left upper limb fat rate,left lower limb The indexes of fat volume,fat rate of left lower limb,fat amount of upper right limb,fat rate of upper right limb,fat amount of right lower limb and fat rate of right lower limb were significantly higher than those of TTTCT genotype carriers(P<0.05).In Tibetan women,in addition to the torso fat rate and right lower limb fat rate of the two indicators,the other indicators of TCT missing individuals are significantly higher than TTTCT genotype carriers(P<0.05),with TCT purity missing individuals the highest,TCT hybrid missing individuals second.Compared with the normal group,there was a significant difference in the frequency of genotype distribution of MC4 R gene rs71336392 sites(P<0.05),and the incidence of TCT deficiency mutation was higher in the obesity group.3.SH2B1 gene rs7359397 site obesity group genotype distribution frequency CC:51.4%,CT:37.1%,TT:11.4%,normal genotype distribution frequency CC:62.2 9%,CT:35.7%,TT:1.4%,allele distribution frequency C:80.7% and T:19.3%,all in line with Hardy-Weinberg’s law,with group representation.The weight,BMI,fat content,body fat rate,visceral fat content,subcutaneous fat content,torso fat content,torso fat rate,left upper limb fat content,left upper limb fat rate,left lower limb fat amount,left lower limb fat rate,right upper limb fat content,right upper limb fat rate,right upper limb fat rate,right lower limb fat amount,The fat rate of the right lower limb was significantly higher than that of CC genotype carriers(P<0.05),with TT genotype carriers being the highest and CT genotype carriers second,and there was no difference between the obese-related indicators of Tibetan women(P>0.05).Compared with the normal group,there were significant differences in the frequency of GEnotype distribution and allele distribution frequency of SH2B1 gene rs7359397 in Tibetan male obesity group(P<0.05),and the incidence of TT genotype and T allele was higher in the obesity group.4.NEGR1 gene rs3101336 site obesity group genotype distribution frequency TT: 2.9%,TC: 24.3%,CC: 72.9%;In Tibetans,there was no difference in obesity-related indicators among the three genotypes of the NEGR1 gene rs3101336 site(P>0.05).Compared with the normal group,there was no difference between the frequency of NEGR1 gene rs3101336 site genotype distribution and the frequency of allele distribution.5.There is an interaction between the MC4 R gene rs17782313 site and the SH2B1 gene rs7359397 site in obesity(P<0.05).High-risk group model MC4 R rs17782313-SH2B1 rs7359397 Model 1:(TC)-(CC)and model 2:(TC)-CT carriers are 15.583 times more likely to be obese than carriers of other genotypes(P<0.05),which is a risk factor for obesity.The risk group models MC4 R rs17782313-SH2B1 rs7359397 model 1:(TT)-(CC)and model 2:(TT)-(CT)carriers were 0.050 and 0.059 times(P<0.05)carriers of other genotype carriers,respectively,and were protective factors of obesity.Conclusions1.The MC4 R gene rs17782313 site and rs71336392 site can be used as molecular genetic markers of obesity in Tibetans;The SH2B1 gene rs7359397 site can be used as a molecular genetic marker for male obesity in Tibetans,and the NEGR1 gene rs3101336 site is not related to obesity in Tibetans.2.There is an interaction effect in obesity between the MC4 R gene rs17782313 site and the SH2B1 gene rs7359397 site,and different genotype combinations have different effects on obesity.