CAJ | 학술논문

目的：研究褪黑激素受体1B （MTNR1B）基因rs4753426位点单核苷酸多态性（SNP）在妊娠期糖尿病（ GDM）孕妇与健康孕妇之间基因型及等位基因频率的差异，以及与GDM发病的相关性。方法选择2011年7月至2012年7月青岛大学附属医院GDM孕妇93例（ GDM组），同期选取健康孕妇165例为对照组。记录两组孕妇的年龄、孕周、身高、早孕期体质量，并计算体质指数（BMI），检测两组孕妇空腹胰岛素（ FIN）、空腹血糖（ FPG）水平；以 PCR 及 DNA 测序技术检测MTNR1B基因rs4753426位点SNP基因型频率和等位基因频率；比较分析两组孕妇基因型频率、等位基因频率、FPG、FIN、BMI 及稳态模型评估的胰岛素抵抗指数（ HOMA-IR ）、胰岛β细胞功能指数（HOMA-β）的差异。结果（1）GDM组孕妇CC、CT和TT基因型频率分别为72.0％（67／93）、21.5％（20／93）和6.5％（6／93），T、C等位基因频率分别为17.2％（32／186）、82.8％（154／186）；对照组CC、CT和TT基因型频率分别为53.9％（89／165）、40.0％（66／165）和6.1％（10／165），T、C等位基因频率分别为26.1％（86／330）、73.9％（244／330）；GDM组与对照组间MTNR1B基因rs4753426基因型频率及等位基因频率分别比较，差异均有统计学意义（P＜0.05）。（2）GDM组孕妇的FPG、FIN、HOMA-IR水平高于对照组，差异均有统计学意义（ P＜0.05）；HOMA-β则较对照组降低，差异有统计学意义（P＜0.05）。（3）GDM组内CC及CT基因型孕妇FPG水平高于TT基因型孕妇，HOMA-β则低于TT基因型者，分别比较，差异均有统计学意义（P＜0.05）。结论 MTNR1B基因rs4753426位点SNP与GDM的发病相关，该位点可能是GDM发病的易感位点，C等位基因是GDM的易感基因。
목적：연구퇴흑격소수체1B （MTNR1B）기인rs4753426위점단핵감산다태성（SNP）재임신기당뇨병（ GDM）잉부여건강잉부지간기인형급등위기인빈솔적차이，이급여GDM발병적상관성。방법선택2011년7월지2012년7월청도대학부속의원GDM잉부93례（ GDM조），동기선취건강잉부165례위대조조。기록량조잉부적년령、잉주、신고、조잉기체질량，병계산체질지수（BMI），검측량조잉부공복이도소（ FIN）、공복혈당（ FPG）수평；이 PCR 급 DNA 측서기술검측MTNR1B기인rs4753426위점SNP기인형빈솔화등위기인빈솔；비교분석량조잉부기인형빈솔、등위기인빈솔、FPG、FIN、BMI 급은태모형평고적이도소저항지수（ HOMA-IR ）、이도β세포공능지수（HOMA-β）적차이。결과（1）GDM조잉부CC、CT화TT기인형빈솔분별위72.0％（67／93）、21.5％（20／93）화6.5％（6／93），T、C등위기인빈솔분별위17.2％（32／186）、82.8％（154／186）；대조조CC、CT화TT기인형빈솔분별위53.9％（89／165）、40.0％（66／165）화6.1％（10／165），T、C등위기인빈솔분별위26.1％（86／330）、73.9％（244／330）；GDM조여대조조간MTNR1B기인rs4753426기인형빈솔급등위기인빈솔분별비교，차이균유통계학의의（P＜0.05）。（2）GDM조잉부적FPG、FIN、HOMA-IR수평고우대조조，차이균유통계학의의（ P＜0.05）；HOMA-β칙교대조조강저，차이유통계학의의（P＜0.05）。（3）GDM조내CC급CT기인형잉부FPG수평고우TT기인형잉부，HOMA-β칙저우TT기인형자，분별비교，차이균유통계학의의（P＜0.05）。결론 MTNR1B기인rs4753426위점SNP여GDM적발병상관，해위점가능시GDM발병적역감위점，C등위기인시GDM적역감기인。
Objective To investigate the genotypic and allele frequency differences of melatonin receptor 1B (MTNR1B)-rs4753426 between gestational diabetes mellitus (GDM) pregnancies and normal pregnancies , and to explore the association between single nucleotide polymorphism ( SNP ) of rs4753426 and gestational diabetes mellitus.Methods Totally 93 GDM pregnancies and 165 normal pregnancies were recruited from the Affiliated Hospital of Qingdao University.The age, gestational weeks, height, early pregnant weight , and the levels of fasting plasma glucose ( FPG) , fasting insulin ( FIN) were determined in every participants.By using PCR and DNA sequencing , we detected the distribution of the rs 4753426 genotypes and alleles in all individuals.The homeostasis model assessment-insulin resistance ( HOMA-IR) and the homeostasis model assessment-βcell function ( HOMA-β) were calculated.The allele and genotype frequencies and the FPG , FIN, body mass index ( BMI) , HOMA-IR, HOMA-βlevels between GDM group and control group were compared.Results (1) The genotype frequencies in the GDM group and the control group of rs4753426-CC, CT, TT were 72.0% (67/93), 21.5% (20/93), 6.5% (6/93), and 53.9%(89/165), 40.0% (66/165), 6.1% (10/165) respectively.The allele frequencies in the GDM group and the control group of T and C were 17.2% ( 32/186 ) , 82.8% ( 154/186 ) and 26.1% ( 86/330 ) , 73.9% ( 244/330 ) respectively.There were statistical differences in genotype frequencies and allele frequencies between two groups ( all P<0.05 ).( 2 ) The levels of FPG , FIN and HOMA-IR in the GDM group were obviously higher than those in the control group (P<0.05).The level of HOMA-βwas lower in the GDM group than that of the control group (P<0.05).(3)The FPG of CC and CT genotypes was higher than that of TT genotype in the GDM group (P<0.05), while the level of HOMA-βwas lower than that of TT genotype (P<0.05).Conclusions The MTNR1B-rs4753426 SNP is associated with the pathogenesis of GDM, and rs4753426 is the predisposing locus of GDM.The C-allele is the susceptibility allele of GDM.