| Objective: The pathogenesis of gestational diabetes mellitus is still unclear.This study explores the relationship between JNK signaling pathway gene polymorphisms and gestational diabetes,and provides clues for the pathogenesis of gestational diabetes.Methods: The individuals was selected from the Taiyuan Birth Cohort Program(TBCP).Collect the general situation of pregnant women who delivered their babies at the First Hospital of Shanxi Medical University from March 2012 to July 2014.334 pregnant women were diagnosed with GDM,as case.334 non-gestational diabetes pregnant women were matched as the control group according to the same age,the same place of residence and the difference of pregnancy time no more than 3 months.Among them,28 subjects were excluded because the genotyping deletion rate exceeded 10%.Finally,321 subjects in the gestational diabetes group and 319 subjects in the control group.The pregnancy and birth history,the information of the birth control,the history of previous illness and pregnancy-related diseases,individuals Lifestyle and habits,clinical diagnosis and auxiliary examination results,fetal growth and development,and birth outcomes were also collected.Face-to-face surveys were conducted using a standardized structured questionnaire to collect questionnaire information within 24 hours of delivery.5 ml of anticoagulant mother blood was collected before delivery.Single Nucleotide Polymorphism site typing was performed on the Illumina Goldengate Platform.For statistics,Chi-square test determines whether the SNP locus in the JNK signaling pathway conforms to the Hardy-Weinberg equilibrium law.,the association between gene and GDM is analyzed by min P test.An unconditional logistic regression model was used to test the relationshio between gene polymorphism and GDM.The OR value and 95% are calculated.Letter interval.Haploview 4.2 was used to construct haplotypes.Results: After the Hardy-Weinberg equilibrium law,there were 10 genes and 134 SNP sites in this pathway.Adjusting the body mass index and family history of diabetes.The following genetic polymorphisms were positively associated with lower risk of GDM: MAP4K4rs6543018 genotype GG was 0.41 times than genotype AA(OR=0.41,95% CI 0.16-0.95).MAP3K2rs7565286 genotype GA was 0.42 times than genotype GG(OR=0.42,95% CI 0.20-0.84);GA & AA genotype was 0.39 times than GG genotype(OR=0.39,95% CI 0.18-0.77).The AG genotype at rs62159921 was 0.40 times than AA genotype(OR=0.40,95% CI 0.17-0.86);the AG & GG genotype was 0.34 times the risk of AA genotype(OR=0.34,95% CI 0.15-0.74).The AG genotype at rs10175150 was 0.42 times than AA genotype(OR=0.42,95%CI 0.18-0.88);AG & GG genotype was 0.37 times than AA genotype(OR=0.37,95%CI 0.16-0.76).The GA genotype at the rs6710365 was 0.34 times than GG genotype(OR=0.34,95% CI 0.15-0.72);the GA & AA genotype was 0.33 times than GG genotype(OR=0.33,95%CI 0.14-0.69).The AG genotype at the rs6707983 was 0.33 times than the AA genotype(OR=0.33,95% CI 0.14-0.69);the AG & GG genotype was 0.32 times than the AA genotype(OR=0.32,95%)CI 0.14-0.67).The MAP3K1rs55993418 TA genotype was 0.61(OR=0.61,95% CI 0.41 – 0.92)than the TT genotype;TA & AA genotype was 0.59 times than the TT genotype(OR=0.59,95% CI 0.40 – 0.88).The rs79640283 GA genotype was 0.39 times than the GG genotype(OR=0.39,95% CI 0.19 – 0.76).The GA genotype at rs11745858 was 0.62(OR=0.62,95% CI 0.40 – 0.94)than the GG genotype;GA & AA genotype was 0.60 times than the GG genotype(OR=0.60,95% CI0.40 – 0.91).The AT genotype at rs990453 was 0.63 times than the AA genotype(OR=0.63,95% CI 0.41 – 0.97);the AT& TT genotype was 0.61 times than the AA genotype(OR=0.61,95% CI)0.40 – 0.94).The MAPK8rs12573325 GA genotype was 0.69 times than the GG genotype(OR=0.69,95% CI 0.48 – 0.99);GA & AA genotype was 0.67 times than the GG genotype(OR=0.67,95%CI 0.47 – 0.95).The rs7089288 GG genotype was 0.56 times than the risk of AA genotype(OR=0.56,95% CI 0.32 – 0.97);the AG & GG genotype was 0.70 times than the AA genotype(OR=0.70,95% CI0.51 – 0.97).The following genetic polymorphisms were positively associated with higher risk of GDM: MAP4K4rs11694166 GA genotype is 1.55 times than the genotype GG(OR=1.55,95% CI 1.10 – 2.17),GA & AA genotype is 1.44 times than the GG(OR=1.44,95% CI 1.05 – 1.98).MAP3K2rs6747825 CA & AA genotype was 1.61 times than the CC genotype(OR=1.61,95% CI 1.1 – 2.38).The MAP3K1rs9292139 AC genotype was 1.44 times than the AA genotype(OR=1.44,95% CI 1.01 – 2.06);CC genotype was 1.92 times than the AA genotype(OR=1.92,95% CI)1.21 – 3.07);The AC & CC genotype was 1.56 times than the AA genotype(OR=1.56,95% CI 1.12 – 2.19).The rs2968214 AA genotype was 1.72 times than the CC genotype(OR=1.72,95% CI 1.07 – 2.78);the CA & AA genotype was 1.42 times than the CC genotype(OR=1.42,95%CI 1.03 – 1.97).The rs13172186 AA genotype was 2.51 times than the GG genotype(OR=2.51,95% CI 1.22 – 5.47).The MAPK9rs61321448 AG genotype was 2.49 than the AA genotype(OR=2.49,95% CI 1.09 – 6.21).The rs144057417 AC genotype was 1.47 times than the AA genotype(OR=1.47,95% CI 1.02 – 2.11).The AG genotype at the rs2619756 was 1.80 times than the AA genotype(OR = 1.80,95% CI 1.04-3.18).There are four blocks on the JNK pathway that have an impact on the risk of GDM.MAKP8 rs79047287 rs2125067 rs1902724 block haplotype G-G-C was 0.67 times than the risk of G-G-A(OR=0.67,95% CI 0.49 – 0.93).MAP3K1 rs16887069 rs9292139 block haplotype G-C was 0.73 times than the risk of haplotype G-A(OR=0.73,95% CI 0.54 – 0.89).MAP3K1 rs2968214 rs17688329 rs11745858 block haplotype C-G-A was 1.49 times than the risk of haplotype C-G-G(OR=1.49,95% CI 1.08 – 2.11);haplotype A-G-G was 1.41 times than the risk of haplotype C-G-G(OR=1.41,95% CI 1.13 – 2.17).MAPK8 rs12573325 rs76351820 rs7100244 rs7089288 haplotype A-G-G-G was 1.46 times than the risk of G-G-G-A(OR=1.46,95%CI:1.25 – 1.76).Conclusion: JNK signaling pathway MAP4K4(rs6543018 rs11694166),MAP3K2(rs7565286 rs62159921 rs10175150 rs6710365 rs6707983 rs6747825),MAP3K1(rs55993418 rs79640283 rs11745858 rs990453 rs9292139 rs2968214 rs13172186),MAPK8(rs12573325 rs7089288)and MAPK9(rs61321448 rs61321448 The rs2619756)genetic polymorphisms were associated with the risk of GDM,suggesting that JNK signaling pathway plays a role in the pathogenesis of GDM. |
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