AIP基因在散发性泌乳素型垂体腺瘤中的单核苷酸多态性分析
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摘要
目的探讨芳烃受体相互作用蛋白(AIP)基因在散发性泌乳素型垂体腺瘤中的单核苷酸多态性(SNPs)。方法回顾性分析2008年9月至2018年8月收治的43例散发性泌乳素型垂体腺瘤患者(实验组)及43例健康人(对照组)的临床资料,并留取其外周血样本进行聚合酶链式反应,同时分别提取AIP基因外显子的DNA进行测序,对比分析两组样本中AIP基因的SNPs差异。所有实验均重复三次。结果实验组中共有8例(18.6%)患者被检测出存在5种不同的SNPs,分别为7051C>T(第4外显子序列,由C突变为T,其基因型为CT杂合型);7318C>A(第5外显子序列,由C突变为A,其基因型为CA杂合型);7886A>G(第6外显子序列,由A突变为G,其基因型为AG杂合型);8012G>C及8020G>C(第6外显子序列,由G突变为C,其基因型为GC杂合型)。其所相应编码的氨基酸均无改变。对照组43例样本中均未检测出SNPs。结论尽管AIP基因的SNPs在散发性泌乳素型垂体腺瘤中被检测出,但由于该基因出现SNPs的概率较低,因而初步判定该基因的SNPs与该型肿瘤的发生无明显相关性。
Objective To investigate the single nucleotide polymorphisms(SNPs)of aryl hydrocarbon receptor interacting protein(AIP) gene in sporadic prolactin pituitary adenomas.Methods The clinical data of 43 patients with sporadic prolactin-type pituitary adenoma(experimental group) and 43 healthy volunteers(control group) admitted from September 2008 to August 2018 were retrospectively analyzed.Peripheral blood samples were collected for polymerase chain reaction.DNA in exons of AIP gene was extracted for sequencing.SNPs of AIP gene were analyzes and compared between two groups.All the experiments were repeated three times.Results In experimental group,8 patients(18.6%) were identified to have five different SNPs:7051 C>T(exon-4 sequence,mutated from C to T,CT heterozygous genotype),7318 C>A(exon-5 sequence,mutated from C to A,CA heterozygous genotype),7886 A>G(exon-6 sequence,mutated from A to G,AG heterozygous genotype),8012 G>C and 8020 G>C(exon 6 sequence,mutated from G to C,GC heterozygous genotype).No change was found in the corresponding coding amino acids.No SNPs in AIP gene were identified in control group.Conclusions Although SNPs of AIP gene can be detected in sporadic prolactin-type pituitary adenomas,low probability of SNPs appears in this gene.Therefore,it is judged preliminarily that mutations in AIP gene might not have an important role in the occurrence of sporadic prolactin-type pituitary adenomas.
Objective To investigate the single nucleotide polymorphisms(SNPs)of aryl hydrocarbon receptor interacting protein(AIP) gene in sporadic prolactin pituitary adenomas.Methods The clinical data of 43 patients with sporadic prolactin-type pituitary adenoma(experimental group) and 43 healthy volunteers(control group) admitted from September 2008 to August 2018 were retrospectively analyzed.Peripheral blood samples were collected for polymerase chain reaction.DNA in exons of AIP gene was extracted for sequencing.SNPs of AIP gene were analyzes and compared between two groups.All the experiments were repeated three times.Results In experimental group,8 patients(18.6%) were identified to have five different SNPs:7051 C>T(exon-4 sequence,mutated from C to T,CT heterozygous genotype),7318 C>A(exon-5 sequence,mutated from C to A,CA heterozygous genotype),7886 A>G(exon-6 sequence,mutated from A to G,AG heterozygous genotype),8012 G>C and 8020 G>C(exon 6 sequence,mutated from G to C,GC heterozygous genotype).No change was found in the corresponding coding amino acids.No SNPs in AIP gene were identified in control group.Conclusions Although SNPs of AIP gene can be detected in sporadic prolactin-type pituitary adenomas,low probability of SNPs appears in this gene.Therefore,it is judged preliminarily that mutations in AIP gene might not have an important role in the occurrence of sporadic prolactin-type pituitary adenomas.
引文
[1] Lim CT,Korbonits M.Update on the clinicopathology of pituitary adenomas[J].Endocr Pract,2018,24(5):473-488.
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[8] Hu Y,Yang J,Chang Y,et al.SNPs in the aryl hydrocarbon receptor-interacting protein gene associated with sporadic non-functioning pituitary adenoma[J].Exp Ther Med,2016,11(3):1142-1146.
[9] Daly AF,Jaffrain-Rea ML,Ciccarelli A,et al.Clinical characterization of familial isolated pituitary adenomas[J].J Clin Endocrinol Metab,2006,91(9):3316-3323.
[10] Daly AF,VanbellinPRLen JF,Khoo SK,et al.Aryl hydrocarbon receptor-interacting protein gene mutations in familial isolated pituitary adenomas:analysis in 73 families[J].J Clin Endocrinol Metab,2007,92(5):1891-1896.
[11] DiGiovanni R,Serra S,Ezzat S,et al.AIP Mutations are not identified in patients with sporadic pituitary adenomas[J].Endocr Pathol,2007,18(2):76-78.
[12] Georgitsi M,Heli?vaara E,Paschke R,et al.Large genomic deletions in AIP in pituitary adenoma predisposition[J].J Clin Endocrinol Metab,2008,93(10):4146-4151.
[13] Igreja S,Chahal HS,Akker SA,et al.Assessment of p27 (cyclin-dependent kinase inhibitor 1B) and aryl hydrocarbon receptor-interacting protein (AIP) genes in multiple endocrine neoplasia (MEN1) syndrome patients without any detectable MEN1 gene mutations[J].Clin Endocrinol (Oxf),2009,70(2):259-264.
[14] Ozfirat Z,Korbonits M.AIP gene and familial isolated pituitary adenomas[J].Mol Cell Endocrinol,2010,326(1/2):71-79.
[15] Chahal HS,Stals K,Unterl?nder M,et al.AIP mutation in pituitary adenomas in the 18th century and today[J].N Engl J Med,2011,364(1):43-50.
[2] Rostomyan L,Beckers A.Screening for genetic causes of growth hormone hypersecretion[J].Growth Horm IGF Res,2016(30/31):52-57.
[3] Demir H,Donner I,Kivipelto L,et al.Mutation analysis of inhibitory guanine nucleotide binding protein alpha (GNAI) loci in young and familial pituitary adenomas[J].PLoS One,2014,9(10):e109897.
[4] Wang S,Lin K,Xiao D,et al.The Relationship between posterior pituitary bright spot on magnetic resonance imaging (MRI) and postoperative diabetes insipidus for pituitary adenoma patients[J].Med Sci Monit,2018,24:6579-6586.
[5] Toledo RA,Mendonca BB,Fragoso MC,et al.Isolated familial somatotropinoma:11q13-loh and gene/protein expression analysis suggests a possible involvement of aip also in non-pituitary tumorigenesis[J].Clinics (Sao Paulo),2010,65(4):407-415.
[6] Asa SL,Casar-Borota O,Chanson P,et al.From pituitary adenoma to pituitary neuroendocrine tumor (PitNET):an International Pituitary Pathology Club proposal[J].Endocr Relat Cancer,2017,24(4):C5-C8.
[7] Agustsson TT,Baldvinsdottir T,Jonasson JG,et al.The epidemiology of pituitary adenomas in Iceland,1955-2012:a nationwide population-based study[J].Eur J Endocrinol,2015,173(5):655-664.
[8] Hu Y,Yang J,Chang Y,et al.SNPs in the aryl hydrocarbon receptor-interacting protein gene associated with sporadic non-functioning pituitary adenoma[J].Exp Ther Med,2016,11(3):1142-1146.
[9] Daly AF,Jaffrain-Rea ML,Ciccarelli A,et al.Clinical characterization of familial isolated pituitary adenomas[J].J Clin Endocrinol Metab,2006,91(9):3316-3323.
[10] Daly AF,VanbellinPRLen JF,Khoo SK,et al.Aryl hydrocarbon receptor-interacting protein gene mutations in familial isolated pituitary adenomas:analysis in 73 families[J].J Clin Endocrinol Metab,2007,92(5):1891-1896.
[11] DiGiovanni R,Serra S,Ezzat S,et al.AIP Mutations are not identified in patients with sporadic pituitary adenomas[J].Endocr Pathol,2007,18(2):76-78.
[12] Georgitsi M,Heli?vaara E,Paschke R,et al.Large genomic deletions in AIP in pituitary adenoma predisposition[J].J Clin Endocrinol Metab,2008,93(10):4146-4151.
[13] Igreja S,Chahal HS,Akker SA,et al.Assessment of p27 (cyclin-dependent kinase inhibitor 1B) and aryl hydrocarbon receptor-interacting protein (AIP) genes in multiple endocrine neoplasia (MEN1) syndrome patients without any detectable MEN1 gene mutations[J].Clin Endocrinol (Oxf),2009,70(2):259-264.
[14] Ozfirat Z,Korbonits M.AIP gene and familial isolated pituitary adenomas[J].Mol Cell Endocrinol,2010,326(1/2):71-79.
[15] Chahal HS,Stals K,Unterl?nder M,et al.AIP mutation in pituitary adenomas in the 18th century and today[J].N Engl J Med,2011,364(1):43-50.