Endoplasmic reticulum aminopeptidase 1 and genetic susceptibility to pre-eclampsia / 中华围产医学杂志

Objective:To investigate whether endoplasmic reticulum aminopeptidase 1 ( ERAP1) is a susceptible gene for pre-eclampsia (PE) and the possible mechanism in the pathogenesis. Methods:This retrospective study included 990 PE patients (case group) and 1 240 healthy pregnant women (control group) in six prefecture-level tertiary hospitals in Shandong Province, including the Affiliated Hospital of Qingdao University and Zaozhuang Maternal and Child Health Hospital, from September 2018 to April 2021. Peripheral blood were collected for DNA extraction. Single-nucleotide polymorphisms in the ERAP1 gene (rs30187, rs27044, and rs469783 loci) were analyzed by Taqman probe polymerase chain reaction (PCR). Two missense mutant plasmids, rs30187(c.1583A>G) and rs27044(c.2188C>G), were constructed by point mutation induction based on wild-type plasmids. Six groups (knock-down control, knock-down, over-expression control, over-expression, variant 1 and 2 groups) were set up in this study. After transfecting Htr8 cells with different transfection molecules, the expression of ERAP1 at mRNA and protein levels were detected. Besides, the effects of different transfections on cell function were detected using Transwell migration assay, Transwell invasion assay, cell scratch assay, and CCK-8 assay. Statistical analysis was performed using two independent samples t-test, rank sum test, and Chi-square test. Results:(1) There were significant differences in the genetic distribution of rs30187 (Genotype: χ2=29.25, Allele: χ2=4.68) and rs469783 (Genotype: χ2=7.01, Allele: χ2=6.45) as well as the genotype distribution of rs27044 ( χ2=28.95) between the case group and the control group (all P<0.05). Statistical analysis of the genetic model revealed that rs30187 and rs27044, both recessive models, were statistically different between the two groups with a higher frequency of CC genotypes in the case group ( χ2=20.82 and 19.97, both P<0.05), but a lower frequency in CC dominant gene pattern for rs469783 ( χ2=5.82, P=0.016). (2) Compared with the knock-down control group, the knock-down group showed significantly inhibited expression of ERAP1 (mRNA: 0.5±0.1 vs 1.0±0.0, t=7.49; protein: 0.4±0.1 vs 0.7±0.1, t=2.81; both P<0.05), reduced cell migration rate after 48 h of scratching [(16.5%±1.8%) vs (23.8%±2.4%), t=3.33, P=0.031] and decreased number of cells crossing Transwell chambers after 24 h of culture (423.7±21.3 vs 499.0±24.6, t=3.29, P=0.031). Compared with the over-expression group, variant 1 group and variant 2 group showed significantly inhibited expression of ERAP1 at mRNA (both P<0.001) and protein ( P=0.003 and 0.006) levels after transfection, decreased number of cells crossing Transwell chambers ( P=0.001 and 0.032) and down-regulated cell migration rate after 48 h of scratching [variant 1: P=0.004; variant 2: (21.1±4.6)% vs (28.3±1.1)%, t=2.10, P=0.099]. ERAP1 expression at both mRNA ( P<0.001) and protein ( P=0.008) levels, as well as cell proliferation ( P<0.001) and invasion ability ( P<0.001), were all enhanced in the over-expression group than those in the over-expression control group. Moreover, the migration rate of cells after 48 h of scratching ( P=0.002) and the number of cells crossing Transwell chambers after 24 h of culture ( P=0.001) were also increased. Conclusions:The rs30187, rs27044, and rs46978 on ERAP1 gene were all associated with PE susceptibility, with more carriers of the CC genotype in PE patients at rs30187 and rs27044 loci and more carriers of the CC genotype in healthy gravida at rs469783 locus. ERAP1 may be involved in the pathogenesis of PE by affecting the migratory and invasive ability of trophoblast cells.

Association study on vitamin D receptor gene polymorphisms and Tourette syndrome / 中华行为医学与脑科学杂志

Objective:To investigate the association between gene polymorphisms in vitamin D receptor(VDR) and Tourette syndrome (TS).Methods:The genetic contributions of VDR FokI (rs2228570), BsmI (rs1544410), and Cdx2 (rs11568820) polymorphisms were genotyped by TaqMan allelic discrimination real-time (RT)-PCR, which evaluated by a case-control analysis in 417 TS patients and 442 healthy controls, and followed by a family-based study in 417 TS trios.Chi-square test and relative risk analysis were conducted by IBM SPSS 23.0 software.Results:FokI (rs2228570) had three genotypes(CC=109, CT=235, TT=73); BsmI (rs1544410) had three genotypes(AA=2, AG=45, GG=370); Cdx2 (rs11568820) had three genotypes(AA=71, AG=200, GG=146). No significant difference in genotype ( χ2=5.516, P=0.063; χ2=3.466, P=0.177; χ2=0.561, P=0.755, respectively) or allele frequencies( χ2=0.840, P=0.359; χ2=3.376, P=0.066; χ2=0.051, P=0.822, respectively)of FokI, BsmI and Cdx2 were identified between TS patients and control groups.No significant over-transmission was identified for these three polymorphisms among 417 TS trios in the family-based study (TDT for FokI: χ2=0.009, P=0.962; for BsmI: χ2=1.220, P=0.320; and for Cdx2: χ2=0.260, P=0.646). Haplotype relative risk (HRR) analysis and haplotype-based haplotype relative risk (HHRR) analysis showed no significant difference in allele frequencies distribution of FokI, BsmI and Cdx2 (all P>0.05). Conclusion:VDR receptor gene polymorphism has no effect on TS susceptibility in the Chinese Han population. However, a potential role of VDR should be explored in more polymorphisms, different populations and larger samples.

Clinical Significance of Detection of ZIC1 Promoter Methylation in Peripheral Blood and Cancer Tissues of Non-small Cell Lung Cancer Patients / 肿瘤防治研究

Objective To investigate the methylation status of ZIC1 gene in peripheral blood and lung cancer tissues of NSCLC patients and its prognostic significance. Methods We took the peripheral blood, cancer tissues and adjacent tissues of 95 NSCLC patients. The peripheral blood of 95 healthy people was taken as control group. MSP was used to compare the detection rate of ZIC1 methylation between peripheral blood and cancer tissues. And we analyzed the correlation of ZIC1 methylation in peripheral blood and cancer tissues with the clinicopathological factors of NSCLC patients. Results The methylation detection rates of ZIC1 in peripheral blood and lung cancer tissues in NSCLC patients were significantly higher than those in peripheral blood of healthy people and adjacent tissues of NSCLC patients (P < 0.05), and the sensitivity and specificity of ZIC1 methylation in the diagnosis of tumor tissues were higher. The positive rate of ZIC1 gene methylation in peripheral blood and tumor tissues of NSCLC patients was significantly correlated with tumor diameter, metastasis, stage and pleural effusion (P < 0.05). Conclusion The methylation of ZIC1 gene is related to the occurrence, development, metastasis and stage of NSCLC. It may be used as a diagnostic and prognostic indicator of NSCLC.

Expression of lncRNA MIR210HG in preeclampsia placental tissue and its functional analysis / 中华妇产科杂志

Objective:To investigate the differential expression of long non-coding RNA (lncRNA) in placental tissues of women with preeclampsia (PE) and the effect of MIR210HG on the biological function of HTR8/SVneo cells.Methods:A total of 39 cases of PE women (PE group) and 39 cases of normal pregnant women (CTL group) admitted to the Affiliated Hospital of Qingdao University from July 2018 to July 2019 were collected. (1) Transcriptome sequencing (RNA-seq) was used to analyze the differentially expressed lncRNAs in the placental tissues of the two groups. (2) The expression level of MIR210HG, one of the differentially expressed lncRNAs, in the placental tissues of the two groups was detected by real-time quantitative PCR. And the correlations between the expression level of MIR210HG and systolic blood pressure, diastolic blood pressure and neonatal birth weight were analyzed. (3) The constructed small interfering RNA and negative control (NC) RNA were transfected into the HTR8/SVneo cells. The cells were divided into MIR210HG knockdown (KD) group and NC group. The effects of living cell counting (CCK-8) and transwell assay on the proliferation and migration of HTR8/SVneo cells were detected. (4) RNA interacting with MIR210HG was predicted using the Encyclopedia of RNA Interactomes (ENCORI) database. Gene Ontology (GO) functional annotation, Kyoto Encyclopedia of Gene and Genomes (KEGG) and BioCarta pathway enrichment analysis were performed.Results:(1) A total of 26 significantly differentially expressed lncRNAs were found by RNA-seq, among which 21 lncRNAs were up-regulated and 5 lncRNAs were down-regulated. (2) The relative expression level of MIR210HG in the PE group was significantly higher than that in the CTL group (9.30±1.90 and 1.10±0.20, respectively; t=4.425, P<0.01). The relative expression level of MIR210HG had positive linear correlation with systolic blood pressure ( r2=0.234, P<0.05) and diastolic blood pressure ( r2=0.190, P<0.05), but had a negative linear correlation with newborn birth weight ( r2=0.157, P<0.05). (3) Compared with the NC group, the proliferation and migration ability of HTR8/SVneo cells in the KD group were increased (all P<0.05). (4) A total of 38 RNAs that might interact with MIR210HG were predicted by ENCORI database. GO functional annotation analysis showed that MIR210HG might be involved in the functions of 27 pathways, including the regulation of production of molecular mediator of immune response, etc; KEGG pathway analysis showed that MIR210HG might be involved in the function of 8 pathways including allograft rejection, etc; Biocarta pathway analysis showed that MIR210HG may be involved in the functions of 8 pathways, including the eukaryotic initiation factor (eIF) pathway, etc. Conclusion:The expression of MIR210HG is up-regulated in the placental tissue of PE women, and MIR210HG might be a regulator of the biological behavior of trophoblast cells.

Study on GLIS3 mutations in children with congenital hypothyroidism / 中华实用儿科临床杂志

Objective To investigate the features and characteristics of GLIS3 gene mutation in patients with congenital hypothyroidism(CH),and to establish the theoretical basis for gene diagnosis and prenatal diagnosis of CH.Methods Genomic DNA was extracted from peripheral blood leukocytes of 50 patients with CH who were collected from February 2007 to November 2016 in Shandong Province.The exon 2 to 11 of GLIS3 were amplified with 11 pairs of sequence specific primers designed by Primer 5.0.Polymerase chain reaction and the first generation of sequencing method(Sanger sequencing) were used to detect the mutation.Comparison of the sequencing results with the GLIS3 reference sequence (National Center for Biotechnology Information Reference Sequence:NC_000009.12) helped to screen gene mutations.Results The 50 CH patients included 22 boys and 28 girls,and the sex ratio was 1.0 ∶ 1.3.The mean age was (2.5 ± 0.5) years.Six cases (12％) had thyroid gland hypoplasia,23 cases (46％) had thyroid gland agenesis and 21 cases(42％) with ectopic thyroid gland.C2507A missense mutation was found in exon 10 of GLIS3 in a thyroid gland agenesis case,which might result in proline to glutamine substitution at codon 836.One mutant (rs780019691,c.C289T) was detected which was nonsense mutation (Arg→Stop) in another thyroid gland agenesis child.Conclusions The mutation rate of GLIS3 gene is very low in CH children of Shandong province.Further studies are needed to investigate the relationship between GLIS3 genotypes and clinical phenotypes.

GRIN3B gene mutation screening in children with Tourette syndrome / 中华实用儿科临床杂志

Objective To explore the association between the GRIN3B gene and Tourette syndrome (TS) in children by screening mutations in the coding region of this gene.Methods Fifty-one children with TS and their parents in the Affiliated Hospital of Qingdao University from October 2015 to November 2016 were selected as an experimental group,41 cases of boys,and 10 cases of girls,aged 6-16 years[(9.78 ±3.64)years],while 60 people aged 22-45 years in the health examination center were selected in the control group,49 cases were male,1 1 cases were female,aged 22-45 years [(29.08 ± 2.89) years].DNA was extracted from 51 patients with TS,their parents and 60 controls.PCR was applied to amplify the encoding region of GRIN3B gene and Sanger sequencing was used to sequence,then GRIN3B sequencing results were compared with the NCBI gene encoding region sequence (NM_138690.2)to test whether these patients carried gene mutation and to verify the findings from their family.Results c.C460T gene variant of GRIN3B was found in 2 patients (p.P154S);c.T1187C (p.L396S) variant of GRIN3B gene was found in 10 patients and both of abnormal GRIN3B sites lead to changes in amino acid.The 2 peak sequencing maps were obtained by Sanger sequencing but nothing was found in their parents.Conclusion The mutation of GRIN3B gene may be related to the development of TS.

Association of rs1013940 polymorphism in SLC5A7 with Tourette syndrome in Chinese Han popula-tion / 中华行为医学与脑科学杂志

Objective To investigate the association between rs1013940 in SLC5A7 and Tourette Syndrome ( TS) in Chinese Han population.Methods Polymorphism was genotyped in 401 TS nuclear fam-ilies trios from china by real-time fluorescent quantitive PCR.Transmission disequilibrium test ( TDT) and Haplotype relative risk ( HRR ) were used to analyze the association between the genetic distrbution of rs1013940 and TS and the results were verified by haplotype-based haplotype relative risk( HHRR) .Results No transmission disequilibrium was found between rs1013940 in SLC5A7 and TS by TDT and HRR( TDT:χ2=0.268, P=0.657, OR=0.728,95%CI=0.366-1.451;HRR:χ2=0.111, P=0.739, OR=0.959,95%CI=0.762-1.466) .HHRR also indicated the same result ( HHRR:χ2=0.276, P=0.599, OR=1.082,95%CI=0.806-1.453) .Conclusion The result reveals that there is no significant association between rs1013940 in SLC5A7 and TS in Chinese Han population.However,the results need to be further validated in different populations.

Study on dual oxidase maturation factor 1 gene mutations in patients with congenital hypothyroidism combined with thyroid goiter / 中华实用儿科临床杂志

Objective To screen the dual oxidase maturation factor 1 (DUOXA1) gene mutations in children with congenital hypothyroidism (CH) and thyroid goiter from Shandong Province,China,and to identify the gene mutation type and characteristics of DUOXA1 gene mutations in order to provide some evidence for gene diagnosis and therapy of CH.Methods A cohort of 52 cases of CH with thyroid goiter and 100 normal controls were selected according to neonatal screening system in Shandong Province whose genomic DNA was isolated from peripheral blood leukocytes with a standard phenol chloroform method.The whole coding sequence (CDS) of DUOXA1 gene was amplified with 8 pairs of sequence specific primers by using PCR.The PCR products were directly sequenced with Sanger sequencing to detect new mutations types of DUOXA1 gene.The sequencing data were compared to the DUOXA1 gene reference sequence(National Center for Biotechnology Information:RefSeq:NG_033105.1) to see if there was any mutation.Ax2 test was done for the gene frequency of discovered single nucleotide polymorphisms (SNP).Results There was no mutation in CDS of 52 CH patients with thyroid goiter and 100 normal controls.However,a SNP (rs75981505,c.398G ＞ T) which was an missense mutation and could lead to a change of the codon from CGC to CTC,was found in 9 CH patients with thyroid goiter and 11 normal controls in the exon 7.The corresponding amino acid arginine was replaced by histidine(p.Arg133His).There was no significant difference in the SNP rate between CH patients with thyroid goiter and normal controls (17.3％ vs 11.0％,x2 =1.24,P ＞ 0.05).Conclusion DUOXA1 gene mutation rate is very low which may not be the main cause of CH patients with thyroid goiter in the population of Shandong Province.

Screening of thyroid hormone receptor β mutations in patients with congenital hypothyroidism combined with thyroid dysgenesis / 中华实用儿科临床杂志

Objective To study the thyroid hormone receptor β(TRβ)gene mutation types and characteristics in children with congenital hypothyroidism(CH)and thyroid dysgenesis(TD)from Shandong Province,and to provide theoretical basis for gene diagnosis and prenatal diagnosis. Methods Sixty cases of TD patients of which genomic DNA were isolated from peripheral blood leukocytes were selected by neonatal screening system in Shandong Province. The exon 6 to 12 of TRβ gene were amplified with 8 pairs of sequence specific primers using PCR and the first generation of sequencing method(Sanger method)to detect mutation. The sequencing results were compared with the TRβ gene reference sequence[National Center for Biotechnology Information(NCBI)Reference Sequence:NC 000003. 12]to see whether there was a mutation. Results Analysis of TRβ in 60 cases of CH patients with TD revealed no mutation was demonstrated in exons 6 - 12,but 2 single nucleotide polymorphism(SNP)( rs 3752874,c. 735C ﹥ T;rs79220627, c. 162G ﹥ A)were detected. Through the analysis,the 2 SNP were all synonymous mutations(Phe→Phe;Ser→Ser), without the change of the amino acids. Conclusions TRβ mutation rate is very low,which may not be the main mutation type in CH patients with TD in Shandong Province.

Relationship between vitmin D receptor rs2228570 polymorphism and susceptibility to gout in Chinese Han male population / 中华内分泌代谢杂志

Objective To explore gene polymorphism of G/A genotype of Fok Ⅰ rs2228570 (G/A) of vitamin D receptor (VDR) gene in Han male population of Chinese coastal area,and thus to investigate the relationship between the gene polymorphism of VDR and gout.Methods Altogether 504 gout patients and 523 healthy controls were enrolled.The possible association between the polymorphism of VDR rs2228570 and gout in Chinese coastal area was investigated and genotype frequencies and allelic frequencies were calculated by realtime PCR with Taqman(R)probe method.Hardy-Weinberg was used to verify the representativeness of the sample.Comparison between the groups were performed withx2 test and t-test.Results The frequencies of GG,AG,and AA genotypes were 32.1％,50.0％,and 17.9％,respectively among gout patients,while they were 27.9％,50.5％,and 21.6％ respectively among the controls.There was no statistically significant difference in VDR rs2228570 genotype frequencies between gout patients and controls(x2 =3.366,P＞0.05).The allele frequencies of G and A in gout cases were different from those in the controls(57.1％,42.9％;53.2％,46.8％;x2 =3.300,P＞0.05).Conclusions Results of the present study suggest that the G/A genotype of VDR Fok Ⅰ rs2228570 of the VDR gene is not associated with gout in male population of Chinese coastal area.

Relationship between interleukin-33 rs3939286A/G polymorphism and gout susceptibility in Shandong male population / 中华风湿病学杂志

Objective The aim of this study was to inve-stigate the associations between genetic variants in interleukin (IL)-33 and susceptibility to gout.Methods The genetic distributions of rs3939286 were detected in 1 100 men with gout and 1 227 ethnically matched controls using Taqman allelic discrimination real-time polymerase chain reaction (PCR).Hardy-Weinberg was used to verify the representativeness of the samples.Differences in genetic distributions between groups were investigated using x2 tests.The genotypephenotype relationship among gout patients was tested by analysis of variance.Results The frequencies of AA,AG and GG genotypes were1,101 and 998 (0.1％,9.2％ and 90.7％) among gout patients,while they were 1 132 and 1 094 (0.1％,10.7％ and 89.2％) among the controls.There were no significant differences in genetic distributions of IL-33 rs3939286 polymorphism between gout patients and controls (P=0.478 by genotype,x2=1.46,P=0.309 by allele).Conclusion Our results have revealed that the rs3939286 variant in IL-33 gene may be not involved in the development of gout in male gout patients of Shandong.However,further studies in other ethnic groups are needed to confirm the results.

Association of serotonin transporter linked polymorphic region 44 bp variable number of tandem repeat polymorphism with Tourette syndrome / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the association between the serotonin transporter linked polymorphic region (5-HTTLPR) 44 bp variable number of tandem repeat (VNTR) polymorphism and Tourette syndrome (TS) in ethnic Han Chinese trios.</p><p><b>METHODS</b>A total of 252 TS trios (patients and their parents) were recruited. Genetic contribution of the 5-HTTLPR 44 bp VNTR polymorphism was evaluated by genotyping, haplotype relative risk (HRR) analysis and transmission disequilibrium test (TDT) statistics. To enhance the efficiency of the test, haplotype-based HRR (HHRR) was also performed.</p><p><b>RESULTS</b>The TDT, HRR and HHRR analyses have revealed a significant association of the 5-HTTLPR 44 bp VNTR polymorphism with TS, and provided a strong evidence for an over-transmission of L allele from parents to the affected children (TDT: χ² = 6.680, df= 1, P= 0.012; HRR: χ² = 9.345, P= 0.002, OR= 1.739, 95% CI for 1.218-2.483). For 204 male and 48 female TS trios, TDT and HRR were analyzed separately. The results showed a significant association between 5-HTTLPR and male TS (for males. TDT: χ² = 4.643, df= 1, P= 0.038; for females, TDT: χ² = 2.189, df= 1, P= 0.188).</p><p><b>CONCLUSION</b>5-HTTLPR may be the susceptibility gene for male TS patients among the Chinese Han population. However, the results need to be replicated in datasets collected from different populations.</p>

Association between single nucleotide polymorphism of rs4753426 of melatonin receptor 1B gene and gestational diabetes mellitus / 中华妇产科杂志

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.

Mutation analysis of STK11 gene in patients with Peutz-Jeghers syndrome / 中华皮肤科杂志

Objective To study the mutation of STK11 gene in a Chinese family and a sporadic patient with Peutz-Jeghers syndrome (PJS),and to provide a basis for genetic diagnosis and counseling.Methods One sporadic patient and two patients from a family with PJS were collected,all of whom had typical mucosal pigmentation and gastrointestinal polyposis.Blood samples were obtained from the two patients and six unaffected relatives in this family,the sporadic patient,and 100 healthy controls.DNA was extracted,and PCR was performed to amplify nine exons and their adjacent introns in the STK11 gene followed by direct sequencing.The sequencing results were aligned to the published sequence of STK11 gene from Genbank.Results No mutation was found in the STK11 gene of any of the patients,unaffected relatives,or healthy controls.Conclusions Genetic heterogeneity exists in Peutz-Jeghers syndrome,hinting that there may be other causative genes or sites for this entity.

Relationship between macrophage migration inhibitory factor-173G/C polymorphism and susceptibility to gout in Chinese male population / 中华风湿病学杂志

Objective To explore gene polymorphism of the G/C genotype of-173G/C(rs755622)in the promoter of macrophage migration inhibitory factor(MIF)gene in male population,and thus to investigate the relationship between gene polymorphism of MIF and gout.Methods A total of 380 gout patients and 378 healthy controls were enrolled.The possible association between the polymorphism of MIF-173G/C and gout in Chinese were investigated and genotype frequencies and allelic frequencies were analyzed by polymerase chain reaction with sequence-specific primers(PCR-SSP)method.Hardy-Weinberg was used to verify the representativeness of the samples.Comparisons between the groups were performed with x2 test.The gene polymorphism of MIF and gout was performed by t test.Results The frequencies of GG,GC,CC genotypes were 62.1％(236 cases),34.2％(130 cases)and 3.7％(14 cases),respectively among gout patients,while they were 66.5％(252 cases),29.8％(113 cases)and 3.7％(14 cases),respectively among the controls.There was no statistical difference in MIF-173G/C genotype frequencies between gout patients and controls(x2=1.713,P=0.425).The allele frequencies of G and C in gout cases were 79.2％(602 cases)and 20.8％(158cases),while the controls were 81.4％(617 cases)and 18.6％(141 cases),and no significant difference between them could be found(x2=1.148,P=0.302).Combine GG and GC of gout into GG+GC,the association analysis of the two groups showed that,mean age,leves of glucose,TG,TC,BUN,Cr and UA of the GG+GC group and the CC group were(51±13)and(50±15)t=0.369,P=0.712;(7.1±8.8)and(6.1±1.2)mmol/L,t=0.352,P=0.725;(2.3±1.6)and(2.9±3.4)mmol/L,t=-1.207,P=0.228;(5.3±1.2)and(5.7±1.4)mmol/L,t=-1.207,P=0.228;(5.8±2.9)and(6.2±2.2)mmol/L,t=-0.513,P=0.608;(92±52)and(84±17)μmol/L,t=0.537,P=0.592;(472±103)vs(557±154)μmol/L,t=-2.949,P=0.03 respectively;no significant difference was found in the two group.Moreover,no association between MIF-173G/C genotypes and risk factors for gout were detected in gout cases by t-test.Conclusion Results of the present study suggest that the G/C genotype of-173G/C in the promoter of MIF gene is not associated with gout in male population.

Association between single nucleotide polymorphism of macrophage migration inhibitory factorrs1007888 and the pathogenesis of gestational diabetes mellitus / 中华妇产科杂志

Objective To investigate the association between single nucleotide polymorphism (SNP) of macrophage migration inhibitory factor (MIF) gene-rs1007888 and the pathogenesis of gestational diabetes mellitus (GDM).Methods A total of 120 GDM pregnant women (GDM group) and 165 healthy pregnant women (control group) from Affiliated Hospital of Medical College,Qingdao University were recruited from June 2011 to July 2012.Their age,gestational week,height and weight were recorded.The levels of fasting blood glucose (FBG) and fasting insulin (FIN) were determined.Body mass index (BMI),the hemeostasis model assessment-insulin resistance (HOMA-IR) and hemeostasis model assessment-β cell function (HOMA-β) were calculated.DNA was extracted from fasting blood samples.SNP of MIFrs1007888G/A was determined by DNA sequencing.The FBG,FIN,HOMA-IR and HOMA-β were compared between GDM group and the control group.They were also compared among pregnancies withdifferent genotypes.Results (1) GDM group had higher FBG,FIN and HOMA-IR levels,but lower HOMA-β than the control group (all P ＜ 0.05).(2) MIF-rs1007888 SNP genotype frequencies of GG,GA and AA were 37.5％,45.8％ and 16.7％,and the allelic frequencies of G and A were 60.4％,39.6％ in GDM group; However,in the control group,the frequencies of GG,GA and AA were 26.1％,54.5％ and 19.4％,and the allelic frequencies of G and A were 53.3％,46.7％,respectively.The distributions of MIF genotypes in GDM patients were significantly different from the healthy subjects (P ＜ 0.05).No significant difference of MIF-rs1007888 allele distributions was observed between GDM group and the control group (P ＞0.05).(3) The FBG,FIN and HOMA-IR in pregnant women with GG genotype were statistically higher than those with GA or AA genotypes,while HOMA-β was lower in women with GG genotype (all P ＜0.05).Conclusions The SNP of MIF rs-1007888 was related to the insulin resistance and pancreatic β cell function of pregnant women.GG genotype of MIF-rsl007888 might be a genetic susceptible factor in the pathogenesis of GDM.

Genetic association of 5-HTR2A 102 T/C polymorphism with Tourette syndrome in a family-based association study in a Chinese Han population / 中华行为医学与脑科学杂志

Objective To investigate whether polymorphism of 102 T/C in 5-HTR2A (serotonin receptor 2A) are associated with Tourette syndrome (TS) in Chinese Han population or none.Methods A total of 101 TS patients and their parents were recruited for the study.The genetic contributions of the 5-HTR-2A 102 T/C polymorphism in 5HTR2A were evaluated using polymerase chain reaction and restriction enzyme digestion (PCRRFLP) and haplotype relative risk (HRR) and transmission disequilibrium test (TDT) statistics.Results The results revealed no significant associations between the 5-HTR-2A 102 T/C polymorphism and TS (HTR-2A 102T/C,TDT =0.353,df=1,P =0.621 ;HRR =1.127,x2 =0.358,P =0.550,95％ CI:0.762-1.666).Conclusion The data suggest that the HTR-2A 102 T/C polymorphism may not be associated with susceptibility to TS in the Chinese Han population.However,these results need to be replicated using larger datasets collected from different populations.

Relationship between interleukin-1β-511C/T polymorphism and susceptibility to gout in Chinese male population / 中华风湿病学杂志

Objective To explore gene polymorphism of the C/T genotype of rs 16 944 in the promoter of IL-1β gene in male population living in the coastal area of Shandong,and thus to investigate the relationship between the gene polymorphism of IL-1β and gout.Methods A total of 276 gout patients and 268 healthy controls were enrolled.The possible association between the polymorphism of IL-1β-511 C/T and gout in Chinese was investigated and gcnotype frequencies and allelic frequencies were calculated by polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP) method.Hardy-Weinberg was used to verify the representativeness of the sample.Comparisons between the groups were performed with x2 test and t-test.Results There was no statistically difference in IL-1β-511 C/T genotype frequencies between gout patients and controls(x2=3.251,P=0.197,df=2).The allele frequencies of C and T in gout cases were not different from those in the controls (x2=2.941,P=0.086,OR=1.232,95％CI:0.971-1.563).Moreover,no association between IL-1β-511C/T genotypes and risk factors for gout were observed in gout cases by x2 test.Conclusion Results of the present study suggest that the C/T genotype of rs 16944 in the promoter of IL-1β gene is not associated with gout in male population living in the coastal area of Shandong.

Relationship between interleukin-1β -31C/T polymorphism and susceptibility to gout in Chinese male population / 中华风湿病学杂志

Objective To explore gene polymorphism of the C/T genotype of rs1143627 in the promoter of IL-1β gene in male population living in the coastal area of Shandong, and thus to investigate the relationship between the gene polymorphism of IL-1β and gout. Methods A total of 208 gout patients and 210 healthy controls were enrolled. The possible association between the polymorphism of IL-1 β -3 1C/T and gout in Chinese were investigated and genotype frequencies and allelic frequencies was calculated by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method. Hardy-Weinberg was used to verify the representativeness of the sample. Comparisons between the groups were performed with χ2 test and t-test. Results The frequencies of CC, CT, and TT genotypes were 32.7%, 43.3% and 24.0%,respectively among gout patients, while they were 31.9%,46.2% and 21.9%, respectively among the controls.There was no statistically difference in IL-1β -31C/T genotype frequencies between gout patients and controls (χ2=0.427, P>0.05). The allele frequencies of C and T in gout cases were different from those in the controls (54.3%, 55.0%; 45.7%, 45.0%; χ2=0.038, P>0.05). Moreover, no association between IL- I β-31 C/T genotypes and risk factors for gout were observed in gout cases by χ2 test. Conclusion Results of the present study suggest that the C/T genotype of rs1143627 in the promoter of IL-1β gene is not associated with gout in male population living in the coastal area of Shandong.

Clinical and magnetic resonance imaging findings in a family with hereditary spastic paraplegia with mutation in NIPA1 / 中华神经科杂志

Objective To study features of the MRI and clinic in a family with pure hereditary spastic paraplegia (PHSPG) type 6.Methods Target loci (SPG3, 4, 6, 8 10 and 12) linkage analysis was performed in a SPG pedigree having 6 affected individuals using microsatellite markers and NIPA1 gene was screened for mutation by PCR-amplification and sequencing. MRI of brain and cervical and thoracic spinal cord were examined in these 6 patients and 6 normal controls matched for age and sex by two independent radiologists blinded to the clinical diagnosis. Cross-sectional areas and anteroposterior and transverse diameters of the spinal cord at the levels of C2～3, C7, T1～4, T9 were measured and data was statistically analyzed using the student's t test. Results A missense mutation of 316g→c in NIPA1 was identified in the affected subjects, presumably resulting in substitution of glutamic acid for arginine in residue 106. Evaluation of the brain MRI images revealed non-specific brain abnormalities. All patients presented thinning of cervical and upper thoracic spine with atrophy in both gray and white matter and enlarged subarachnoid cavity. In severe atrophic segments, a distinct boundary between grey and white matter was observed and the lesions in grey matter presented literal high intensity spots or patches with clear boundary on transaxial T2-weighted images (T2WI) and high signal intensity longitudinal strip on the sagittal T2WI. Cross-sectional areas and anteroposterior and transverse diameters of the spinal cord at C2～3, C7, T1～4 were significantly smaller in patients than in controls, while at the T9 level only transverse diameter showed significant difference (7.22±0.08 vs 8.17±0.41, t=2.870, P=0.046). Conclusions These findings indicate that the disease process in patients with SPG6 might be confined to the cervical and thoracic spinal cord, with atrophy in both white and grey matter having a distinct boundary.