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1.
Journal of Stroke ; : 350-360, 2023.
Article in English | WPRIM | ID: wpr-1001588

ABSTRACT

Background@#and Purpose We investigated the causal relationships between the gut microbiota (GM), stroke, and potential metabolite mediators using Mendelian randomization (MR). @*Methods@#We leveraged the summary statistics of GM (n=18,340 in the MiBioGen consortium), blood metabolites (n=115,078 in the UK Biobank), and stroke (cases n=60,176 and controls n=1,310,725 in the Global Biobank Meta-Analysis Initiative) from the largest genome-wide association studies to date. We performed bidirectional MR analyses to explore the causal relationships between the GM and stroke, and two mediation analyses, two-step MR and multivariable MR, to discover potential mediating metabolites. @*Results@#Ten taxa were causally associated with stroke, and stroke led to changes in 27 taxa. In the two-step MR, Bifidobacteriales order, Bifidobacteriaceae family, Desulfovibrio genus, apolipoprotein A1 (ApoA1), phospholipids in high-density lipoprotein (HDL_PL), and the ratio of apolipoprotein B to ApoA1 (ApoB/ApoA1) were causally associated with stroke (all P<0.044). The causal associations between Bifidobacteriales order, Bifidobacteriaceae family and stroke were validated using the weighted median method in an independent cohort. The three GM taxa were all positively associated with ApoA1 and HDL_PL, whereas Desulfovibrio genus was negatively associated with ApoB/ApoA1 (all P<0.010). Additionally, the causal associations between the three GM taxa and ApoA1 remained significant after correcting for the false discovery rate (all q-values <0.027). Multivariable MR showed that the associations between Bifidobacteriales order, Bifidobacteriaceae family and stroke were mediated by ApoA1 and HDL_PL, each accounting for 6.5% (P=0.028) and 4.6% (P=0.033); the association between Desulfovibrio genus and stroke was mediated by ApoA1, HDL_PL, and ApoB/ApoA1, with mediated proportions of 7.6% (P=0.019), 4.2% (P=0.035), and 9.1% (P=0.013), respectively. @*Conclusion@#The current MR study provides evidence supporting the causal relationships between several specific GM taxa and stroke and potential mediating metabolites.

2.
Frontiers of Medicine ; (4): 1068-1079, 2023.
Article in English | WPRIM | ID: wpr-1010829

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic has stimulated tremendous efforts to develop therapeutic agents that target severe acute respiratory syndrome coronavirus 2 to control viral infection. So far, a few small-molecule antiviral drugs, including nirmatrelvir-ritonavir (Paxlovid), remdesivir, and molnupiravir have been marketed for the treatment of COVID-19. Nirmatrelvir-ritonavir has been recommended by the World Health Organization as an early treatment for outpatients with mild-to-moderate COVID-19. However, the existing treatment options have limitations, and effective treatment strategies that are cost-effective and convenient for tackling COVID-19 are still needed. To date, four domestically developed oral anti-COVID-19 drugs have been granted conditional market approval in China. These drugs include azvudine, simnotrelvir-ritonavir (Xiannuoxin), leritrelvir, and mindeudesivir (VV116). Preclinical and clinical studies have explored the efficacy and tolerability of mindeudesivir and supported its early use in mild-to-moderate COVID-19 cases at high risk for progression. In this review, we discuss the most recent findings regarding the pharmacological mechanism and therapeutic effects focusing on mindeudesivir and other small-molecule antiviral agents for COVID-19. These findings will expand our understanding and highlight the potential widespread application of China's homegrown anti-COVID-19 drugs.


Subject(s)
Humans , Ritonavir/therapeutic use , COVID-19 , Antiviral Agents/therapeutic use , China , Nitriles , Lactams , Proline , Adenosine/analogs & derivatives , Leucine
3.
Chinese Journal of Internal Medicine ; (12): 933-936, 2022.
Article in Chinese | WPRIM | ID: wpr-957665

ABSTRACT

To investigate the clinical and genetic characteristics of patients with idiopathic hypogonadotropic hypogonadism (IHH), the clinical data of 23 patients with IHH were retrospectively analyzed. Gene analyses were accomplished with whole-exome sequencing (WES) and Sanger sequencing. Functional prediction of mutation sites was conducted using two bioinformatics platforms, SIFT and Polyphen. Among the 23 patients with IHH, 9 patients carried prokinin 2 (PROKR2) gene mutations including 4 missense mutations (p.W178S, p.Y113H, p.A103V, p.R164Q), and 1 frameshift mutation (p.D42delinsDED), the remaining 14 cases were found negative in gene sequencing. Functional prediction showed that the above mutations may affect protein function suggestive of a pathogenic role of PROKR2 mutation in the patients. There were no significant differences in the levels of follicle-stimulating hormone, luteinizing hormone, testosterone, and estradiol between the IHH patients with PROKR2 gene mutation and those without. PROKR2 gene mutation might associated with IHH, and the mutations reported in the present study could enrich the pathogenic spectrum of genes.

4.
Chinese Journal of Internal Medicine ; (12): 827-830, 2021.
Article in Chinese | WPRIM | ID: wpr-911446

ABSTRACT

The 17α-hydroxylase/17, 20-lyase deficiency (17-OHD) is a rare disease. The clinical characteristics and gene mutation of 2 late-diagnosed 17-OHD patients with testicular tumor admitted to our hospital from March 2018 to February 2019 were analyzed retrospectively. The two 17-OHD patients were female (46, XY). Laparoscopic abdominal exploration found undeveloped testicles in grey-yellow or grey-red in the groin and iliac fossa. The testicles were removed and showed malignancy in pathology study. Sequencing of the CYP17A1 gene identified c.1247G>A/c.1427T>C and c.985_987delTACinsAA/c.1306G>A complex heterozygous mutations. Taking together, the possibility of 17-OHD should be considered in patients with hypertension, hypokalemia, adrenal adenomatoid hyperplasia together with 46, XY gonadal dysplasia, so as to make early diagnosis and treatment, and avoid dysplastic testicular turning to malignancy.

5.
Chinese Journal of Endocrinology and Metabolism ; (12): 333-336, 2020.
Article in Chinese | WPRIM | ID: wpr-870041

ABSTRACT

Sanger sequencing was applied to analyze the SLC12A3 gene of a patient with suspected Gitelman syndrome(GS) and recurrent spontaneous abortions, as well as for her parents. The results showed that a compound heterozygous mutation(c.1077C>G, c.2890C>T) was found in the proband, which led to the change of amino acid sequence(p.N359K, p.R964W). Among the family members, her mother was a single heterozygotes mutation carrier of c. 1077C>G(p.N359K) and her father had c. 2890C>T(p.R964W) heterozygotes.These results suggest that the GS may cause adverse pregnancy outcomes due to imbalance of internal environment, complex hormonal changes, and electrolyte abnormalities. The pregnancy management should be strengthened.

6.
Chinese Journal of Endocrinology and Metabolism ; (12): 254-258, 2019.
Article in Chinese | WPRIM | ID: wpr-745718

ABSTRACT

Calorie restriction is one of the diet therapies for people with diabetes.Calorie restriction can reduce weight and improve glycemic control,but the long-term effects are controversial.The effects can be influenced by the degree of calorie restriction,the study duration,and the types of food used for intervention.The mechanism includes the improvement of β cell function and insulin sensitivity.The existing problems are compliance of patients,long-term effects,possible adverse effects,and the lack of high-quality studies.In this review,we introduced the current research progress of calorie restriction on glucose metabolism in patients with type 2 diabetes.

7.
Chinese Journal of Medical Genetics ; (6): 120-123, 2019.
Article in Chinese | WPRIM | ID: wpr-775799

ABSTRACT

OBJECTIVE@#To explore the genotype-phenotype correlation among 18 patients with 21-hydroxylase deficiency (21-OHD).@*METHODS@#PCR-Sanger sequencing was used to analyze the 10 exons and flanking regions of the CYP21A2 gene among the 18 patients and 20 healthy controls.@*RESULTS@#Seventeen patients had variants of the CYP21A2 gene. Eight patients (44.4%, 8/18) carried homozygous variants including p.Ile 173Asn (62.5%, 5/8), p.Pro31Leu (25.0%, 2/8), and IVS2-13A/C>G (12.5%, 1/8), respectively. Six patients (33.3%, 6/18) carried compound heterozygous variant, among which IVS2-13 A>G+p.Ile 173Asn were most common (50.0%). 94.4% (34/36) of the variant were pathogenic, with the most common variants being p.Ile173Asn (41.7%), IVS2-13A/C>G (19.4%), and p.Ile173Asn (7.5%). No variant was identified among the 20 healthy controls.@*CONCLUSION@#The majority of 21-OHD patients carried CYP21A2 gene variants in homozygous or compound heterozygous forms, among which the p.Ile173Asn was the most common one. There is a strong correlation between the genotypes and clinical phenotypes.


Subject(s)
Humans , Adrenal Hyperplasia, Congenital , Genetics , Genotype , Mutation , Phenotype , Steroid 21-Hydroxylase , Genetics
8.
Chinese Journal of Medical Genetics ; (6): 877-881, 2019.
Article in Chinese | WPRIM | ID: wpr-776785

ABSTRACT

OBJECTIVE@#To identify pathogenic variants in 5 sporadic patients and two Chinese pedigrees affected with 17-hydroxylase deficiency (17-OHD).@*METHODS@#Peripheral blood samples were collected with informed consent. Variants of CYP17A1 gene were screened by PCR and Sanger sequencing. Suspected mutations were validated in other members of the pedigrees.@*RESULTS@#Gene sequencing has identified a homozygous c.985_987delTACinsAA (Y329Kfs) mutation in exon 6 of the CYP17A1 gene in 4 patients and the sister of case 3. Case 1 was found to harbor compound heterozygous mutations c.1459_1467del9 (p.D487_F489del) and c.1244-3C>A. The parents and brother of cases 2 and 5 were heterozygous carriers of a c.985_987delTACinsAA(Y329Kfs) mutation.@*CONCLUSION@#Mutations of the CYP17A1 gene probably underlie the pathogenesis of 17-OHD, for which c.985_987delTACinsAA(Y329Kfs) is the most common. The c.1244-3C>A is a novel mutation. Above results have facilitated genetic counseling for the affected families.


Subject(s)
Female , Humans , Male , Adrenal Hyperplasia, Congenital , Genetics , Exons , Mutation , Pedigree , Steroid 17-alpha-Hydroxylase , Genetics
9.
Chinese Journal of Medical Genetics ; (6): 877-881, 2019.
Article in Chinese | WPRIM | ID: wpr-797485

ABSTRACT

Objective@#To identify pathogenic variants in 5 sporadic patients and two Chinese pedigrees affected with 17-hydroxylase deficiency (17-OHD).@*Methods@#Peripheral blood samples were collected with informed consent. Variants of CYP17A1 gene were screened by PCR and Sanger sequencing. Suspected mutations were validated in other members of the pedigrees.@*Results@#Gene sequencing has identified a homozygous c. 985_987delTACinsAA (Y329Kfs) mutation in exon 6 of the CYP17A1 gene in 4 patients and the sister of case 3. Case 1 was found to harbor compound heterozygous mutations c. 1459_1467del9 (p.D487_F489del) and c. 1244-3C>A. The parents and brother of cases 2 and 5 were heterozygous carriers of a c. 985_987delTACinsAA(Y329Kfs) mutation.@*Conclusion@#Mutations of the CYP17A1 gene probably underlie the pathogenesis of 17-OHD, for which c. 985_987delTACinsAA(Y329Kfs) is the most common. The c. 1244-3C>A is a novel mutation. Above results have facilitated genetic counseling for the affected families.

10.
Chinese Journal of Geriatrics ; (12): 1069-1072, 2018.
Article in Chinese | WPRIM | ID: wpr-709417

ABSTRACT

Objective To investigate the effect and its underlying mechanism of Linagliptin on mild cognitive impairment (MCI) in elderly type 2 diabetes mellitus (T2DM) patients.Methods Montreal Cognitive Assessment(MoCA)scale was used to prospectively screen T2DM patients for MCI in our hospital from December 2016 to June 2017,and a total of 98 elderly T2DM patients with MCI were recruited.They were randomly divided into the linagliptin group(Linagliptin + metformin,n=50)and the non-linagliptin group(gliclazide + metformin,n =48).Serum fasting plasma glucose (FPG),glycosylated hemoglobin(HbAlc),blood lipids and amyloid β-protein 1-42 (Aβ1-42) levels were determined,and MoCA score and homeostasis model assessment of insulin resistance(HOMA-IR)were calculated,and were compared between the two groups before and after 24 weeks of treatment.Results In the linagliptin group,serum FPG,HbA1c,HOMA-IR,Aβ1-42 levels were significantly decreased and MoCA score was increased after 24 weeks of treatment as compared with pre-treatment [(7.29± 1.00) mmol/L vs.(9.16 ± 1.60) mmol/L,(7.19 ± 0.99) % vs.(9.36 ± 1.07) %,(3.05 ± 1.12) vs.(4.05±1.30),(0.463±0.093)g/L vs.(0.528±0.110)g/L,(24.48± 1.18) vs.(23.22± 1.37),all P<0.05].In the non-linagliptin group as control,FPG and HbA1c levels were decreased after 24 weeks of treatment as compared with pre-treatment[(7.23±1.09)mmol/L vs.(9.20± 1.75) mmol/L,(7.23±1.03)% vs.(9.69± 1.18)%,both P < 0.05],while there was no significant difference in HOMA IR,Aβ1-42 level and MoCA score[(3.95 ± 1.00) vs.(4.19± 1.13),(0.517± 0.113)g/L vs.(0.526±0.119)g/L,(23.21±1.18) vs.(23.00±1.32),all P>0.05].It is worth to pay close attention to the key discovery of this paper that HOMA-IR and Aβ1-42 levels were significantly lower and MoCA score was significantly higher in the linagliptin group than in the non-linagliptin group after 24 weeks of treatment(all P<0.05).Conclusions Linagliptin as one of DPP-4 enzyme inhibitors can improve the cognitive function in elderly patients with T2DM,which might be relevant to reducing serum Aβ level and improving HOMA-IR.DPP-4 enzyme inhibitor may be a good option for treatment of mild cognitive dysfunction in T2DM patients in the future.

11.
Chinese Journal of Endocrinology and Metabolism ; (12): 776-780, 2017.
Article in Chinese | WPRIM | ID: wpr-662661

ABSTRACT

Objective To investigate the influence of blood glucose fluctuation on ser202 phosphorylation sites of tau protein( p-Tau) in hippocampus of diabetic rats; to explore the possible mechanism of blood glucose fluctuation impacting on tau protein hyperphosphorylation. Methods Healthy male Sprague Dawley rats were randomly divided into normal control group ( NC group ) and diabetes group. After diabetic rats model was established, all the diabetic rats were randomly divided into diabetic continuous hyperglycemia group (DC group) and diabetic blood glucose fluctuant group ( DF group). Rats in DF group were given glucose solution intraperitoneal injection twice at regular time everyday. 30 minutes after each intraperitoneal injection, insulin subcutaneously injections were given. Rats in the NC group and DC groups were given the same volume of saline subcutaneous injection. Specimens were collected in 8 weeks, the levels of p-Tau and total tau in rat hippocampus were detected by immunohistochemical staining and Western blotting. The immunoreactive positive products were analyzed by image analysis system. Glycogen synthase kinase-3β(GSK-3β) mRNA was detected by realtime PCR. Results (1) Blood glucose fluctuation of rats in DC and DF group were greater than NC group. And the mean blood glucose, standard deviation of mean blood glucose (SDBG), and large amplitude of glycemic excursion (LAGE) levels were increased significantly compared to NC group, the difference has statistical significance ( all P < 0. 05). Compared with DC group, SDBG and LAGE levels of DF group were higher (both P<0. 05). HbA1C and insulin levels were no difference (P>0. 05). (2) Compared with NC group, the hippocampal p-Tau level of DC group and DF group were increased (P < 0. 05 ); Compared with DC group, the hippocampal p-Tau expression of DF group was increased ( P <0. 05). Compared with DC group, a higher hippocampal GSK-3β mRNA level was found in DF group ( P <0. 05). Conclusions On the basis of diabetes animal model, giving glucose solution intraperitoneal injection and insulin subcutaneously injection 30 minutes later twice at regular time everyday could establish experimental model of diabetic blood glucose fluctuation. Blood glucose fluctuation may aggravate the diabetic rats hippocampal p-Tau. The possible mechanism seems to be an up regulation of the GSK-3β.

12.
Chinese Journal of Geriatrics ; (12): 836-839, 2017.
Article in Chinese | WPRIM | ID: wpr-611150

ABSTRACT

Objective To explore the relationship between visfatin and mild cognitive impairment(MCI)in patients with type 2 diabetes mellitus(T2DM).Methods A perspective study involving 75 hospitalized T2DM patients were divided into groups with(MCI,n=35)and without (NMCI,n =40)mild cognitive impairment.Another 30 non-diabetic patients were chosen as normal control(NC).Fasting plasma levels of glucose (FPG),insulin (FINS),lipid,glycosylated hemoglobin (HbAlc),HOMA-IR and visfatin were measured and calculated.Results The serum visfatin level was higher in MCI(28.81±3.32)μg/L than in NMCI(20.69±3.40)μg/L and NC(19.06±2.35)μg/L (F=96.491,P< 0.01).Visfatin was negatively correlated with Montreal Cognitive Assessment (MoCA) total score (MoCA-TS) (r =-0.646,P < 0.01),but positively correlated with course of disease,waist hip ratio,FPG,HbAlc,FINS,HOMA-IR and triglyceride (r=0.282,0.276,0.318,0.496,0.339,0.433,0.309,P<0.05 or P<0.01).MoCA-TS was negatively correlated with course of disease,HbAlc,HOMA-IR,triglyceride,total cholesterol,low density lipoprotein cholesterol (r =-0.582,-0.365,-0.234,-0.330,0.277,-0.238,P<0.05 or P<0.01),but positively correlated with high density lipoprotein cholesterol(r=0.290,P<0.05).Higher values of visfatin(OR =3.246,P<0.01),HbAlc(OR=2.308,P<0.01)and course of disease(OR=1.634,P<0.05)were the risk factors for MCI.Conclusions The elevated visfatin level might be a risk factor for MCI in T2DM patients.

13.
Chinese Journal of Endocrinology and Metabolism ; (12): 776-780, 2017.
Article in Chinese | WPRIM | ID: wpr-660504

ABSTRACT

Objective To investigate the influence of blood glucose fluctuation on ser202 phosphorylation sites of tau protein( p-Tau) in hippocampus of diabetic rats; to explore the possible mechanism of blood glucose fluctuation impacting on tau protein hyperphosphorylation. Methods Healthy male Sprague Dawley rats were randomly divided into normal control group ( NC group ) and diabetes group. After diabetic rats model was established, all the diabetic rats were randomly divided into diabetic continuous hyperglycemia group (DC group) and diabetic blood glucose fluctuant group ( DF group). Rats in DF group were given glucose solution intraperitoneal injection twice at regular time everyday. 30 minutes after each intraperitoneal injection, insulin subcutaneously injections were given. Rats in the NC group and DC groups were given the same volume of saline subcutaneous injection. Specimens were collected in 8 weeks, the levels of p-Tau and total tau in rat hippocampus were detected by immunohistochemical staining and Western blotting. The immunoreactive positive products were analyzed by image analysis system. Glycogen synthase kinase-3β(GSK-3β) mRNA was detected by realtime PCR. Results (1) Blood glucose fluctuation of rats in DC and DF group were greater than NC group. And the mean blood glucose, standard deviation of mean blood glucose (SDBG), and large amplitude of glycemic excursion (LAGE) levels were increased significantly compared to NC group, the difference has statistical significance ( all P < 0. 05). Compared with DC group, SDBG and LAGE levels of DF group were higher (both P<0. 05). HbA1C and insulin levels were no difference (P>0. 05). (2) Compared with NC group, the hippocampal p-Tau level of DC group and DF group were increased (P < 0. 05 ); Compared with DC group, the hippocampal p-Tau expression of DF group was increased ( P <0. 05). Compared with DC group, a higher hippocampal GSK-3β mRNA level was found in DF group ( P <0. 05). Conclusions On the basis of diabetes animal model, giving glucose solution intraperitoneal injection and insulin subcutaneously injection 30 minutes later twice at regular time everyday could establish experimental model of diabetic blood glucose fluctuation. Blood glucose fluctuation may aggravate the diabetic rats hippocampal p-Tau. The possible mechanism seems to be an up regulation of the GSK-3β.

14.
Chinese Journal of Endocrinology and Metabolism ; (12): 47-51, 2016.
Article in Chinese | WPRIM | ID: wpr-483480

ABSTRACT

Objective To investigate cartilage oligomeric matrix protein( COMP) gene mutation in a three-generation pedigree with two cases of pseudoachondroplasia, and to definitize genotype-phenotype correlation. Methods The clinical data and peripheral blood were collected from the patients with pseudoachondroplasia and their family members. All the 19 exons and their flanking sequences of COMP gene in two patients and three unaffected family numbers and 50 unrelated individuals were analyzed by PCR amplification and direct sequencing. Results The proband, a 6-year-old girl presented with typical clinical features of pseudoachondroplasia, including disproportionate short limb dwarfism, staggering gait, double genu varus deformity, and wider clinical and imaging long bone metaphysis. The 33-year-old father showed a similar manifestation including disproportionate short limb dwarfism and double genu varus deformity, and was performed correcting operation on lower limbs for double genu varus at the age of 10 years. DNA sequencing analysis of the COMP gene revealed a del mutation ( c. 1417 1419delGAC)in exon 13 in two patients with pseudoachondroplasia, but not in the other unaffected members from the pedrgree and 50 control subjects. Conclusion A del mutation c. 1417 1419delGAC of COMP gene may contribute to the disease in the pedigree.

15.
Journal of Modern Laboratory Medicine ; (4): 12-14,17, 2014.
Article in Chinese | WPRIM | ID: wpr-602106

ABSTRACT

Objective To study the clinical characteristics and iduronate-2-sulfatase (IDS)gene mutation of one child patient with mucopolysaccharidosis type Ⅱ (MPS Ⅱ).Methods All the 9 exons of IDS gene were amplified by polymerase chain reaction (PCR)technlogy.The PCR products were screened by direct gene Sanger sequencing.Results A missense muta-tion (c.445T>C)on exon 4 was found after the analysis of the gene sequencing results of PCR products in this patient’s IDS gene.Thi smutation leaded to the 149th codon TCT encoded serine into a CCT encoding proline (p.Ser149Pro).Mean-while,the IDS gene in the parents were widetpye,so this was a de novo mutation.Conclusion The de novo mutation of IDS gene is the cause of our patient with?mucopolysaccharidosis,one novel mutation (p.Ser149Pro)was identified.

16.
Chinese Journal of Medical Genetics ; (6): 289-293, 2014.
Article in Chinese | WPRIM | ID: wpr-254464

ABSTRACT

<p><b>OBJECTIVE</b>To analyze CYP21A2 gene mutation in two families with 21-hydroxylase deficiency (21-OHD) and to explore the correlation between genotype and clinical phenotype.</p><p><b>METHODS</b>Two patients with 21-OHD and their families were investigated. CYP21A2 gene mutation was analyzed by PCR and direct sequencing.</p><p><b>RESULTS</b>The probands from family 1 and 2 have been respectively diagnosed with simple virilizing and non-classical 21-OHD. Both showed increased baseline serum 17hydroxyprogesterone, testosterone and adrenocorticotropic hormone (ACTH), but had no evidence of salt loss. Computer tomography revealed bilateral adrenal hyperplasia in both patients. After 1 year treatment, both had conceived successfully. DNA sequencing revealed that the proband of family 1 had compound heterozygous mutations for IVS2 13 A>G and Ile172Asn. Her father was heterozygous for Ile172Asn, whilst her mother and brother were heterozygous for IVS213A/C>G. In family 2, the proband was heterozygous for Arg341Trp and Gln318X. Her father, sister and nephew were heterozygous for Arg341Trp, whilst her mother was heterozygous for Gln318X. her brother and niece were non-affected. Carriers of single heterozygous mutations in both families had no clinical sign.</p><p><b>CONCLUSION</b>In both families, the disease has been caused by compound heterozygous mutations, for which there has been a good genotype-phenotype agreement. Screening of CYP21A2 gene can facilitate both diagnosis and genetic counseling.</p>


Subject(s)
Adult , Child , Female , Humans , Male , Young Adult , Adrenal Hyperplasia, Congenital , Blood , Genetics , Adrenocorticotropic Hormone , Blood , Base Sequence , Genotype , Molecular Sequence Data , Mutation, Missense , Pedigree , Phenotype , Steroid 21-Hydroxylase , Genetics , Metabolism , Testosterone , Blood
17.
Chinese Journal of Endocrinology and Metabolism ; (12): 647-649, 2012.
Article in Chinese | WPRIM | ID: wpr-424036

ABSTRACT

The clinical and genetic data were retrospectively analyzed in a pedigree with pseudohypoparathyroidism type Ⅰ a.Clinically typical Albright hereditary osteodystrophy (AHO),hypocalcemia,hyperphosphatemia,and PTH- and TSH-resistance were manifested in the proband,but not in his brother and parents.The proband's symptom of epilepsy was alleviated by treatment with calcium and vitamin D,which was of no avail in regard to AHO.After GNAS1 genes were sequenced and compared with the GenBank data among the family members,a deletion of c.1107_1108 ( p.Glu370ArgfsX11 ) in exon l3 of GNAS1 gene leading to a frameshift mutation was found in the proband and his mother.It suggested that the GNAS1 gene mutation might be related to the pathogenesis of the disease.

18.
Chinese Journal of Endocrinology and Metabolism ; (12): 139-143, 2009.
Article in Chinese | WPRIM | ID: wpr-395445

ABSTRACT

Objective To study the association of transcription factor 7-like 2(TCF7L2)polymorphisms with tvpe 2 diabetes mellitus in Chinese Han population. Methods Two polymorphisms (rs7903146 and rs12255372)of TCF7L2 gene were genotyped in 446 patients with type 2 diabetes mellitus(T2DM group)and 303 normal subiects (NC group) by PCR-restriction fragment length polymorphism(PCR-RFLP).Waist circumference.body mass index,plasma glucose,serum insulin,lipid profiles,high-sensitivity C-reactive protein and non-esterified fatty acid were measured.Homeostasis model assessment of insulin resistance(HOMA-IR)and β-cell function(HOMA-β)were calculated.Results (1) In T2DM group,T allele frequency and CT,TY geno tvpe frequeneies of rs7903146 were significantly higher than those in NC group(0.093,0.150,0.018 vs 0.043, 0.079,0.003,respectively,a11 P<O.O 1).Logistic regression analysis showed that the CT/TT genotype was a risk factor of tvpe 2 diabetes(OR=2.25,95%CI 1.39-3.62,P=0.001)and was associated with the decrease of insulin secretion. (2) No significant association was observed in vs12255372 alleles and genotypes with type 2 diabetes mellitus.Conclusion These results indicate that TCF7L2 might be one of the candidate genes for confe ring susceptibi lity to type 2 diabetes mellitus in the Chinese Han population.

19.
Chinese Journal of Medical Genetics ; (6): 681-685, 2009.
Article in Chinese | WPRIM | ID: wpr-349080

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the association of the FcRL3 gene promoter A/G, exon 2 C/G and exon 4 C/T polymorphisms with Graves disease(GD) in Chongqing Han population.</p><p><b>METHODS</b>One hundred and twenty eight GD patients and 120 control subjects from Chongqing Han population were studied for the polymorphisms by PCR-RFLP and DNA direct sequencing; uTSH, FT3, FT4 and/or TT3, TT4, TRAb, TgAb and TPOAb were measured. Pairwise linkage disequilibrium was calculated and haplotypes were estimated by using the unphased 1122 and LDA1.0 softwares. Statistical differences of genotype,allelic and haplotype frequencies were obtained by Chi-square test between the case group and control group.</p><p><b>RESULTS</b>There were significant differences in the genotype and allelic frequencies between the two groups (P<0.05). Frequency of haplotype H1(GG) was significantly higher in patients than that in controls among the three major haplotypes (50.8 vs 35.8, P<0.05). Except family history with the promoter SNP (P<0.05), there was no association between clinical manifestations and FCRL3 polymorphisms in the case group.</p><p><b>CONCLUSION</b>The results of multi-allele and haplotype analysis indicated that the polymorphisms of the promoter A/G,exon 2 C/G,exon 4 C/T in the FcRL3 gene were possible risk factors to GD in Chongqing Han population.</p>


Subject(s)
Adult , Female , Humans , Male , Middle Aged , Asian People , Ethnology , Genetics , Base Sequence , Case-Control Studies , China , Exons , Genetic Predisposition to Disease , Graves Disease , Ethnology , Genetics , Polymorphism, Single Nucleotide , Promoter Regions, Genetic , Receptors, Immunologic , Genetics , Risk Factors
20.
Chinese Journal of Endocrinology and Metabolism ; (12): 149-152, 2008.
Article in Chinese | WPRIM | ID: wpr-401517

ABSTRACT

Objective To investigate the change of serum non-esterified fatty acid (NEFA) level in nondiabetic first-degree relatives of type 2 diabetics, and to explore the related factors in the change.MethodsSerum lipid profile, plasma glucose and insulin levels were measured in 186 type 2 diabetic patients, 565 nondiabetic first-degree relatives of type 2 diabetics and 149 normal controls. Results (1) The fasting NEFA level in first-degree relatives was significantly lower than that of type 2 diabetic patients [(0.53±0.28 vs 0.63±0.31) mmol/L,P<0.01]and HOMA-IR was significantly higher than that of normal controls (0.98±0.51 vs 0.89±0.47,P<0.01). (2) The fasting NEFA level in the first-degree relatives with higher body mass index (BMI), plasma glucose or area under curve of glucose concentration (AUCglu) was higher than that in those with lower BMI, plasma glucose , blood pressure or AUCglu (all P<0.05). (3) NEFA showed significantly positive correlations with BMI, systolic blood pressure, diastolic blood pressure (DBP), AUCglu in the first-degree relatives by correlative analysis (r=0.12, r=0.148, r=0.21 and r=0.281 respectively, all P<0.05). Stepwise linear regression analysis showed that DBP, AUCglu and age were the independent risk factors of NEFA (all P<0.01). Conclusion Insulin resistance exists in nondiabetic first-degree relatives of type 2 diabetics, which seems to be related to elevated NEFA levels.

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