Estudio de frecuencia y asociación de los polimorfismos RS965513 y RS1867277 del gen FOXE1 con el carcinoma papilar de tiroides y su riesgo de recurrencia en población chilena / Frequency and association of the polymorphisms RS965513 and RS1867277 of the FOXE1 gene with papillary thyroid carcinoma and its risk of recurrence in Chilean population

Introducción: El gen FOXE1 (Forkhead box E1) codifica para un factor de transcripción involucrado en la morfogénesis tiroidea. El cáncer papilar de tiroides (CPT) se ha asociado con polimorfismos (SNP) de FOXE1 rs1867277 y rs965513 en población asiática y europea. Nuestro objetivo fue investigar la frecuencia y asociación de SNP rs1867277 y rs965513 con CPT y el riesgo de recurrencia de CPT en sujetos chilenos. Métodos: Se reclutaron sujetos con y sin CPT, se describieron sus características epidemiológicas y la forma de presentación clínica (AJCC VIII y MINSAL 2013). Se aisló ADN de leucocitos periféricos y evaluó ambos SNP mediante PCR-HRM y secuencia. Se compararon las frecuencias alélicas y genotípicas entre casos CPT y controles, y entre pacientes CPT de distintos riesgos de recurrencia. Se compararon frecuencia y se estimó el riesgo con test de Fisher y cálculo de odds-ratio (OR). Resultados: De los 184 sujetos, 156 (85%) eran mujeres, edad 39,3±12,3 años; 90 con CPT y 94 sin CPT 26 (28,9%) pacientes eran de riesgo muy bajo, 45 (50%) bajo, 16 (17,8%) intermedio y 3 (3,3%) alto según MINSAL 2013. En relación a la frecuencia de alelo menor (MAF) calculada en sujetos control y CPT, fue 31,7% y 24,5% (SNP rs965513), y 36,7% y 30,1% 8 (rs1867277), respectivamente (p NS). Tampoco fueron diferentes las MAF calculados y comparados entre pacientes con CPT de riesgo bajo e intermedio/alto. Sin embargo, la combinación de los genotipos rs1867277GG y rs965513AA se asoció a mayor riesgo de CPT. Conclusiones: En pacientes chilenos, se describe una frecuencia MAF de los SNP rs1867277 y rs965513 cercana a un 30%, las cuales no se asocian a CPT ni riesgo de recurrencia, sin embargo, sujetos con una combinación genotípica particular podrían tener mayor riesgo de CPT.

FOXE1 gene (Forkhead E1 box) codes for a transcription factor involved in thyroid morphogenesis. Papillary thyroid cancer (PTC) has been associated with FOXE1 polymorphisms (SNPs) rs1867277 and rs965513 in Asian and European population. Our aim was to investigate the frequency and the association of SNPs rs1867277 and rs965513 with PTC and the risk of recurrence of PTC in Chilean subjects. Methods: We recruited subjects with and without PTC. In those with PTC, their epidemiological characteristics and clinical features presentation are described according to AJCC VIII and MINSAL 2013 scales. Peripheral leukocyte DNA was isolated and both SNPs were evaluated using PCR-HRM and sequencing. Allelic and genotypic frequencies were compared between PTC cases and controls, and between PTC patients with different recurrence risks. Results: Of the 184 subjects, 156 (85%) were women, age 39.3 ± 12.3 years; 94 (51%) without PTC and 90 with PTC (49%): 26 (28.9%) patients had very low, 45 (50%) low, 16 (17.8%) intermediate and 3 (3.3%) high risk of recurence according to MINSAL 2013. Regarding the minor allele frequency (MAF) calculated on control and PTC subjects, was 31.7% and 24.5% (SNP rs965513), and 36.7% and 30.1% (rs1867277), respectively (p NS). In patients with PTC, MAFs were not different between patients with low and intermediate/high risk PTC. However, the combination of rs1867277GG and rs965513AA genotypes were associated with an increased risk of PTC. Conclusions: In Chilean patients, the MAF frequency of SNPs rs1867277 and rs965513 is near 30%, and they are are not associated with PTC or its risk of recurrence. However, subjects with a particular genotypic combination may have an increased risk of PTC.

Association between single nucleotide polymorphisms at LOXL1 promoter and Uygur patients with exfoliation syndrome / 中华实验眼科杂志

Background Exfoliation syndrome (XFS) is a systemic disease with abnormal accumulation of extracellular matrix.Researches showed that the single nucleotide polymorphisms (SNPs) of lysyl oxidase-like 1 (LOXL1) gene is associated with the pathogenesis of XFS in global population.However,the results are varied among different ethnicity and regions.Objective This study aimed to assess the association between LOXL1 gene polymorphisms and XFS in Uygur population.Methods One-hundred and fifty-two Uygur XFS patients without relativeness were enrolled from January to August in 2014,and 228 ethnicity-and gender-matched normal controls were recruited at the same period from the same region.Each individual underwent comprehensive eye examinations and 5 ml peripheral blood was collected.Genomic DNA was extracted from peripheral blood.PCR-ligase detection response (LDR) was used to determine the allele and genotype frequencies of the six SNPs rs12914489,rs4886467,rs4558370,rs4461027,rs4886761 and rs16958477 in the promoter region of LOXL1 gene.The distribution frequency between the patients and normal controls was compared by x2 test.Logistic regression analysis was used for age adjustment.This study was approved by Ethic Committe of Xinjiang Medical University,and informed consent was obtained from the subjects.Results rs12914489 site in the normal control group diverged from Hardy-Weinberg equilibrium (HWE) (P =0.033),and the rs4886467,rs4558370,rs4461027,rs4886761 and rs16958477 sites followed HWE.The frequencies of G allele and GG genotype of rs4886467 in the XFS group were lower than those in the control group (both at P =0.00) and were protective factors of XFS (OR =0.54,95 ％ CI:0.40-0.74,P =0.000;OR=0.51,95％ CI:0.33-0.78,P=0.001);the frequencies of T allele and TT genotype of rs4558370 in the XFS group were significantly higher than those in the control group (both at P=0.00) and were the risk factors of XFS (OR=1.96,95％ CI:1.23-3.11,P =0.004;OR =2.18,95％ CI:1.31-3.64,P =0.002);the frequencies of C allele and CC genotype of rs4461027 in the XFS group were significantly higher than those in the control group (both at P=0.00) and were the risk factors of XFS (OR=2.25,95％ CI:1.67-3.04,P=0.000;OR=3.06,95％ CI:1.89-4.96,P=0.000);the frequencies of T allele and TT genotype of rs4886761 in the XFS group were significantly higher than those in the control group (both at P=0.00) and were the risk factors of XFS (OR=2.44,95％ CI:1.79-3.33,P =0.000;OR =3.02,95％ CI:1.63-5.60,P =0.000);the frequencies of C allele and CC genotype of rs16958477 in the XFS group were significantly higher than those in the control group (both at P=0.00) and were the risk factors of XFS (OR =2.00,95 ％ CI:1.47-2.71,P =0.000;OR =2.37,95 ％ CI:1.31-4.27,P =0.004).Conclusions The SNPs of promoter region of LOXL1 gene are associated with hereditary susceptibility of XFS individually in Uygur population.The SNPs of rs4886467 locus are protective factor,while the SNPs of rs4558370,rs4461027,rs4886761 and rs16958477 locus are risk factors for pathogenesis of XFS.

Polymorphisms of complement genes and ARMS2/HTRAI in patients with age-related macular degeneration in Ningxia, China / 中华实验眼科杂志

Background Age-related macular degeneration (AMD) is the main cause of irreversible loss of central vision in old population.The incidence of AMD is increasing year by year,but the mechanism is not clearly understood.Objective This study was to investigate the association between genetic variants and the risk of AMD in Ningxia population.Methods This study was approved by Ethic Committee of Ningxia People's Hospital and complied with the Helsinki Declaration.Written informed consent was obtained from each subject.One hundred and fifty patients with AMD and 145 ethnicity-and gender-matched controls were recruited in Ningxia Eye Hospital from January 2012 to March 2013.All individuals underwent comprehensive eye examinations and genomic DNA was prepared from peripheral blood.The single nucleotide polymorphisms (SNPs) of 8 susceptibility loci in four candidate genes,including complement factor H (CFH),complement factor B (CFB),age-related maculopathy susceptibility 2 (ARMS2) and high temperature required factor A1 (HTRA1),were genotyped with Mass Array and MALDI-TOF technique by Sequenom platform.The distribution of genotype was tested for Hardy-Weinberge equilibrium (HWE).The differences of genotype distribution of allele and haplotype frequencies were compared between patients and controls using chi-squared test and the P value was significant at ＜ 0.006 level after correction of age,and the relationship of genotype distribution with AMD was evaluated by Logistic regression analysis.Measures of linkage disequilibrium (LD) was carried out by Haploview.Results All the genetypes met HWE.Seven SNPs were found to be different in the genotypic distributions and allele frequencies between patients and normal controls (all at P＜ 0.05),however,after Bonferroni correction,the differences of only four SNPs were significant between the patients and controls in the genotype and allele distributions,including the SNPs of rs10737680 and rs1410996 in CFH gene,the SNP of rs10490924 in ARMS2 gene and SNP of rs11200638 in HTRA1 gene.The allele distributions of rs800292 (Pallele =0.006,OR =1.643,95 ％ CI:1.155-2.336) in CFH and rs641153 (Pallele =0.002,OR =0.273,95 ％ CI:0.120-0.620) in CFB were significantly associated with AMD.In addition,five SNPs in CFH gene were consisted of two blocks after analysis by Haploview.In addition,five SNPs in CFH were consisted of two blocks after analysis by Haploview.The first one SNPs (including rs551397 and rs800292) and another one SNPs (including rs12124794,rs10737680) and rs1410996 were in strong linkage disequilibrium (D'=1.00).After 50 000 permutations,the GC and AT haplotypes of the first block and the AAC,TCT and ACT haplotypes in the second block were significantly different between AMD patients and controls (P =0.010,0.010,0.001,0.041 and 0.033,respectively).The allel T of rs641153 was a protective factor of AMD (P=0.002,OR =0.273,95％ CI:0.120-0.620).Conclusions The SNPs rs10737680 and rs1410996 in CFH,rs10490924 of ARMS2 gene and rs11200638 of HTRA1 gene are associated with AMD in Ningxia population.