Novel mutations of AXIN2 identified in a Chinese Congenital Heart Disease Cohort.

Congenital heart defects (CHDs), the most common congenital human birth anomalies, involves complex genetic factors. Wnt/ß-catenin pathway is critical for cardiogenesis and proved to be associated with numerous congenital heart abnormities. AXIN2 has a unique role in Wnt/ß-catenin pathway, as it is not only an important inhibitor but also a direct target of Wnt/ß-catenin pathway. However, whether AXIN2 is associated with human CHDs has not been reported. In our present study, we found a differential expression of Axin2 mRNA during the development of mouse heart, indicating its importance in mouse cardiac development. Then using targeted next-generation sequencing, we found two novel case-specific rare mutations [c.28 C > T (p.L10F), c.395 A > G (p.K132R)] in the sequencing region of AXIN2. In vitro functional analysis suggested that L10F might be a loss-of-function mutation and K132R is a gain-of-function mutation. Both mutations disrupted Wnt/ß-catenin pathway and failed to rescue CHD phenotype caused by Axin2 knockdown in zebrafish model. Collectively, our study indicates that rare mutations in AXIN2 might contribute to the risk of human CHDs and a balanced canonical Wnt pathway is critical for cardiac development process. To our knowledge, it is the first study of AXIN2 mutations associated with human CHDs, providing new insights into CHD etiology.

A genetic variant in a homocysteine metabolic gene that increases the risk of congenital cardiac septal defects in Han Chinese populations.

Elevated homocysteine levels are known to be a risk factor for congenital cardiac septal defects (CCSDs), but the mechanism underlying this effect is unknown. The genetic variants that were significantly associated with circulating homocysteine concentrations have been systematically identified through the genome-wide association studies of one-carbon core metabolites. To examine the role of the genome-wide significant homocysteine related variants in the occurrence of CCSDs, we investigated the association between these variants and CCSDs in Han Chinese populations. Five variants of the genome-wide significant homocysteine-related genes were selected for analysis in two stages of case-controlled studies with a total of 904 CCSD patients and 997 controls. SYT9 expression was detected in human cardiovascular tissue using qRT-PCR. The intronic variant rs11041321 of the SYT9 gene was associated with an increased risk of developing CCSDs in both the separate and combined case-controlled studies. Combined samples from the two stage cohorts had a significant elevation in CCSD risk for the T allele (OR = 1.43, P = 2.6 × 10-6 ), CT genotype and TT genotype (CT: OR = 1.30, TT: OR = 2.21; P = 1 × 10-4 ) compared with the wild-type C allele and CC genotype, respectively. The risky T allele carriers exhibited decreased SYT9 mRNA expression, compared with wild-type C allele carriers. The intronic SYT9 variant rs11041321, which exhibits a significant genome-wide association with circulating homocysteine, was associated with the occurrence of CCSDs. This finding helps to characterize the unexpected role of SYT9 in homocysteine metabolism and the development of CCSDs, which further highlighted the interplay of diet, genetics, and human birth defects. © 2017 IUBMB Life, 69(9):700-705, 2017.

[Risk factors for different types of hypospadias].

OBJECTIVE: To explore the risk factors for different types of hypospadias. METHODS: According to the 1∶1 ratio, we included hypospadias children in the case group and those without urinary abnormality as controls, all from the Third Affiliated Hospital of Zhengzhou University between October 2015 to October 2016. Using univariate and multivariate logistic regression analyses, we investigated the risk factors for hypospadias as well as for four different types of the disease. RESULTS: Among the 440 subjects, the risk factors for hypospadias included preterm birth, fetal growth restriction, rural residence of the mother, pregnancy age <20 or >35 years, primipara, maternal smoking (including passive smoking), oral progesterone, cold or fever during pregnancy, and exposure to high temperature in early pregnancy, while the protective factors included protein supplement in early pregnancy. The pregnancy age <20 or >35 years was the main risk factor for type I hypospadias; preterm birth, fetal growth restriction, rural residence of the mother, primipara, and maternal smoking (including passive smoking) during pregnancy were the risk factors for type Ⅱ; preterm birth, fetal growth restriction, rural residence of the mother, and exposure to high temperature in early pregnancy were those for type Ⅲ; and exposure to high temperature in early pregnancy and oral progesterone during pregnancy were those for type Ⅳ. CONCLUSIONS: The risk factors for hypospadias vary for different types, and therefore hypospadias-related clinical studies should be conducted and preventive measures should be taken accordingly. However, a larger sample size is needed to get more scientific and reliable results concerning the risk factors for different types of hypospadias.

Association of STAT4 rs7574865 polymorphism with autoimmune diseases: a meta-analysis.

The association between the signal transducer and activator of transcription 4 (STAT4) gene rs7574865 single nucleotide polymorphism and different autoimmune diseases remains controversial and ambiguous. We conducted this study to investigate whether combined evidence shows the association between STAT4 rs7574865 polymorphism and autoimmune diseases. Comprehensive Medline search and review of the references were used to get the relevant reports published before September 2011. Meta-analysis was conducted for genotype T/T (recessive effect), T/T + G/T (dominant effect) and T allele in random effects models. 40 studies with 90 comparisons including 32 systemic lupus erythematosus (SLE), 19 rheumatoid arthritis (RA), 3 type 1 diabetes (T1D), 11 Systemeric Sclerosis (SSc), 4 inflammatory bowed diseases (IBD), 3 Primary Sjogren's syndrome (pSS), 4 juvenile idiopathic arthritis (JIA), 2 Primary antiphospholipid syndrome (APS), 1 Autoimmune thyroid diseases, 1 multiple sclerosis, 1 Psoriasis, 1 Wegener's granulomatosis, 1 Type 2 diabetes, and 1 giant cell arteritis disease were available for this meta-analysis. The overall odds ratios for rs7574865 T-allele significantly increased in SLE, RA, T1D, SSc, JIA, and APS (OR = 1.56, 1.25, 1.13, 1.34, 1.25, and 2.15, respectively, P < 0.00001) and in IBD-UC and pSS (OR = 1.11 and 1.33, respectively, P < 0.05). This meta-analysis demonstrates that the STAT4 rs7574865 T allele confers susceptibility to SLE, RA, T1D, SSc, JIA, APS, IBD-UC, and pSS patients, supporting the hypothesis of association between STAT4 gene polymorphism and subgroup of autoimmune diseases.

Analysis of trends in testicular atrophy index values with age in patients with unilateral palpable cryptorchidism.

Cryptorchidism affects the growth of testicular volume. Testicular volume is associated with reproductive function. The testicular atrophy index evaluates the degree of damage caused by cryptorchidism, but it remains unclear whether changes in testicular atrophy index are related to age. We selected patients who underwent surgery for unilateral palpable cryptorchidism. Testicular volume was measured using ultrasonography. The testicular atrophy indices of the undescended testes were then reviewed, and their correlation with age was analyzed. We studied 228 cases (age range: 6-53 months). Scatter plots were constructed, and Loess curves were fitted, revealing a turning point at 24 months of age. The patients were divided into age groups of 6-24 months and 25-53 months. The testicular volume of the cryptorchid side was smaller than that of the normal side in both groups (both P < 0.001). In the 6-24-month group, the testicular atrophy index was positively correlated with age, testicular volume on the cryptorchid side was not correlated with age, and testicular volume was positively correlated with age on the normal side. In the 25-53-month group, testicular atrophy index and testicular volumes on either side were not correlated with age. A palpable unilateral cryptorchid testis is smaller than the contralateral testis. The testicular atrophy index increases with age between 6 months and 24 months, but not between 25 months and 53 months. Testicular volume increased with age on the normal side between 6 months and 24 months, but not on the cryptorchid side. Trends in testicular atrophy index with age contribute to the decision of operation time.

The CRISPLD2 gene is involved in cleft lip and/or cleft palate in a Chinese population.

BACKGROUND: Nonsyndromic cleft lip and/or cleft palate (NSCLP) are common congenital anomalies in humans, the etiologies of which are complex and associated with both genetic and environmental factors. Previous data suggested single nucleotide polymorphisms (SNPs) of rs1546124, rs4783099, and rs16974880 of the CRISPLD2 gene were associated with an increased risk of NSCLP; however, subsequent studies have yielded conflicting results. This study aims to evaluate the associations of the aforementioned polymorphisms with NSCLP in a Northwestern Chinese population. METHODS: Three CRISPLD2 SNPs were genotyped in a case-control study (n = 907), including 444 NSCLP patients and 463 healthy individuals, using polymerase chain reaction-denaturing high-performance liquid chromatography (PCR-DHPLC). RESULTS: The genotype and allele frequencies of rs1546124 (odds ratio [OR], 2.30; 95% confidence interval [CI], 1.58-3.34; p = 1 × 10(-5) ) and rs4783099 (OR, 0.73; 95% CI, 0.54-1.00; p = 0.05) were different in NSCLP patients compared with controls. Furthermore, the CC genotype at rs1546124 was associated with increased risk for cleft lip with or without cleft palate (CL/P; OR, 2.11; 95% CI, 1.41-3.15; p(correct) = 1.5 × 10(-4) ) and for cleft palate only (CPO; OR, 2.93; 95% CI, 1.69-5.07; p(correct) = 5.4 × 10(-4) ), whereas the T allele of rs4783099 was associated with decreased risk for CPO. Further gender stratification showed that the statistical association of these two loci is mainly in the male patients, and not in female patients. CONCLUSION: Our results suggest that the CRISPLD2 gene contributes to the etiology of NSCLP in the Northwestern Chinese population. SNP rs1546124 is significantly related to NSCLP, associated with both CL/P and CPO groups, and SNP rs4783099 is significantly associated with CPO.

Primary intratracheal schwannoma misdiagnosed as severe asthma in an adolescent: A case report.

BACKGROUND: Primary intratracheal schwannoma is an extremely rare type of benign airway tumor, especially in adolescents. The presenting symptoms are typically prolonged cough and wheezing that can be misdiagnosed as asthma in adolescent patients. CASE: A 16-year-old adolescent girl admitted to a local hospital with symptoms of an irritating cough and wheezing was diagnosed with bronchial asthma and treated with budesonide and formoterol. Over the next year, the patient's wheezing and coughing symptoms gradually worsened and the antiasthma treatment was ineffective. One week prior to this admission, the patient developed dyspnea after catching a cold and was transferred to our hospital with a diagnosis of severe asthma. However, chest computed tomography and bronchoscopy showed a mass in the trachea. Primary intratracheal schwannoma was diagnosed by biopsy. Her symptoms were relieved by endoscopic resection by electrosurgical snaring combined with argon plasma coagulation. No relapse occurred during an 18 mo follow-up. CONCLUSION: Primary intratracheal schwannoma should be considered in the differential diagnosis in adolescents with recurrent asthma-like attacks.

[Effect of Enteromorpha prolifera Biochar on the Adsorption Characteristics and Adsorption Mechanisms of Ammonia Nitrogen in Rainfall Runoff].

In order to study the performance and mechanisms of bioretention pond media (Enteromorpha prolifera biochar) for NH4+-N removal in rainfall runoff, three kinds of alkali modified biochars (marked as BC1, BC2, and BC3) were prepared with various concentrations of NaOH solution (1, 2, and 3 mol·L-1) to explore their adsorption performance for NH4+-N. The results showed that:① Appropriate modifications of the NaOH concentration increased the specific surface area and surface microstructure of biochar, with the content of O and the surface functional groups being enriched. In addition, BC2 possessed the best adsorption performance. ② The adsorption capacity reached a maximum when the pH was 9.0 and the dosage of biochar was 0.5 g·L-1. Compared with BC, the adsorption capacity of BC1 and BC2 increased by 6.4% and 10.8%, respectively, while BC3 decreased by 13.7%. Moreover, BC2 had an optimal adsorption efficiency with a saturated adsorption capacity of 16.76mg·g-1. ③ The adsorption mechanism of biochar belonged to chemical adsorption with a monomolecular layer. The adsorption process was promoted by the high pH of biochar, the electrostatic attraction of biochar pores, the complexation and oxidization of the functional groups of hydroxyl (-OH), carboxyl (-COOH), and carbon-oxygen single bond (C-O). To sum up, the proper amount of NaOH to modify biochar can improve the adsorption performance of NH4+-N, and the modified biochar can be used as media of the bioretention pond to remove NH4+-N.

[Application of denaturing high perfomance liquid chromatography in detection of rpoB mutations associated with rifampin resistance in Mycobacterium tuberculosis].

OBJECTIVE: to explore the value of denaturing high performance liquid chromatography (DHPLC) in detection of rpoB mutations in rifampin-resistant M. tuberculosis, in order to establish a convenient and rapid approach to screening rpoB gene mutations in M. tuberculosis. METHODS: rifampin resistance-determining region of rpoB gene in M. tuberculosis was amplified by PCR and further analyzed by DHPLC to screen mutations at optimized denaturation temperature (65.4 degrees C), which utilized heteroduplex formation between wild-type and mutated DNA strands to identify mutations. The PCR products from strains with different chromatographic profiles were sequenced further to evaluate the sensitivity and specificity. RESULTS: there were 46 M. tuberculosis strains including 42 rifampin resistance strains and 4 rifampin sensitive strains. From these strains, 15 different chromatographic profiles were produced by DHPLC. Combined with the results of gene sequencing, it was shown that strains with different chromatographic profiles had distinct mutations. Except D108 and D24 which had same chromatographic profiles but different genetic polymorphisms, all other strains showed consistent chromatographic profiles with genetic polymorphisms, i.e. if they had identical chromatographic profiles, their genetic polymorphism were the same; but if they had different chromatographic profiles, their genetic polymorphism were also different. CONCLUSION: DHPLC is a simple, efficient, high-throughput and automatic method with high sensitivity and specificity, which may be useful in the rapid detection of rpoB gene mutation in M. tuberculosis.

[Concentration of seminal plasma and serum inhibin B: a predictor in the diagnosis of azoospermia].

OBJECTIVE: To evaluate the concentrations of seminal plasma and serum inhibin B in the differential diagnosis of obstructive and non-obstructive azoospermia. METHODS: We included 37 infertile men with obstructive azoospermia, another 33 with non-obstructive azoospermia and 25 normal fertile men as controls, and measured the concentrations of their FSH serum, seminal plasma and serum inhibin B, using Testicular Histology Johnson Score for the azoospermia infertile men. RESULTS: The concentration ratio of seminal plasma to serum inhibin B was 2.17 in the control and 3.63 in the non-obstructive azoospermia group, with no significant difference (P = 0.29) in between, but obviously lower in the obstructive azoospermia group (0.18), significantly different from the above two (P < 0.01). CONCLUSION: The concentration ratio of seminal plasma to serum inhibin B can be used as a predictor in the diagnosis of obstructive and non-obstructive azoospermia.

[Alpha-glycosidase helps the diagnosis of epididymal obstructive azoospermia].

OBJECTIVE: To assess the diagnostic value of alpha-glycosidase for epididymal lump induced obstructive azoospermia. METHODS: Seventy-six infertile men with normal spermatogenic function were divided according to sperm density into a normal density group (n = 27), an oligospermia group (n = 21) and an obstructive azoospermia group (n = 28), and another 30 fertile males were included as normal controls. Semen plasma alpha-glycosidase, leucocyte count, sexual hormone levels and the diameters of the epididymal lumps were measured and their correlations were analyzed. RESULTS: alpha-Glycosidase in the obstructive azoospermia group was significantly lower than that of the other groups (P <0.05), and negatively correlated with epididymal volume (r = -0.417, P <0.05) and leucocyte count (r = -0.342, P <0.05). CONCLUSION: Alpha-Glycosidase has been proved of diagnostic value for epididymal obstructive azoospermia.

[Analyse of zinc and acid phosphatase in seminal plasma and sperm parameters of infertile male].

OBJECTIVE: This study was to investigate the relationship among zinc, acid phosphatase levels in seminal plasma and sperm parameters in infertile male. METHODS: The activities of zinc and acid phosphatase in seminal plasma were detected and leucocytes was stained and counted in 169 infertile men and 21 normal fertility as control. RESULTS: Acid phosphatase levels in infertile groups were significantly lower than those in the normal control when grouped both in terms of sperm vitality and density( P < 0.01), but no statistical differences were observed among infertile groups (P > 0.05). Further, zinc levels in necrospermia groups were lower than those in the control (P > 0.05). The leucocyte numbers in infertile groups were larger than those in the control when grouped according to sperm density (P < 0.001), and the same results were obtained when grouped in terms of sperm vitality except in the necrospermia group (P > 0.05). Acid phosphatase and zinc levels were not correlated with leucocyte counting (r = 0.088, P = 0.162; r = 0.119, P = 0.057). CONCLUSION: The descent of acid phosphatase and ascent of leucocyte number in seminal plasma can result in the fall of sperm vitality and density, and can be used to be diagnostic indexes of male infertility. Seminal zinc levels in infertile groups were lower than those in the control, but there was no statistical significance.

Association of Wnt3A gene variants with non-syndromic cleft lip with or without cleft palate in Chinese population.

OBJECTIVE: non-syndromic cleft lip with or without cleft palate (NSCLP) is one of the most common birth defects all over the world. Both genetic and environmental factors may contribute to NSCLP. Recent studies have demonstrated that Wnt/ß-catenin signalling pathway is required for lip and palate formation. WNT family may play an important role in the development of NSCLP. This study aimed to evaluate the association between Wnt3A gene polymorphisms and NSCLP in Chinese population from Northwest China. DESIGN: 216 patients with NSCLP and 233 normal controls were genotyped for two SNPs of Wnt3A by PCR-RFLP. Both SNPs genotype frequencies were analysed between cases group and controls group. RESULTS: the frequencies of rs752107 TT and rs3121310 AA were significantly higher in NSCLP cases group (7.4%, 15.3%) than that in controls group (2.1%, 9.5%) with p-value=0.013, 0.014, corrected p value (p-corr) <0.05 and with odds ratio (OR)=3.49, 95% confidence interval [CI]: 1.244-9.79, OR=2.27, 95% CI: 1.17-4.38, respectively; the frequency of rs3121310 GA was also higher in NSCLP cases group (57.4%) than in controls group (52.0%) with p-value=0.042 and OR=1.56 (95% CI: 1.02-2.39). And the frequency of rs752107 TT of Wnt3A showed higher risk in female patients, while the frequency of A allele of rs3121310 showed stronger association in male patients. CONCLUSIONS: this is the first report that two SNPs of Wnt3A (rs752107 and rs3121310) are significantly associated with NSCLP in Chinese population. These findings provide a context for understanding the genetic aetiology of NSCLP.

Signal transducer and activator of transcription 4 gene polymorphisms associated with rheumatoid arthritis in Northwestern Chinese Han population.

AIMS: Signal transducer and activator of transcription 4 (STAT4) gene encode a transcriptional factor that transmits signals induced by several key cytokines which play important roles in the development of autoimmune diseases. Recently, several single nucleotide polymorphisms (SNPs) in STAT4 gene have been reported to be significantly associated with Rheumatoid arthritis (RA) in different ethnic populations. We undertook this study to investigate whether the association of STAT4 genetic polymorphisms with RA is present in Northwestern Chinese Han population. MAIN METHODS: A case-control association study in individuals with RA (n=208) and healthy controls (n=312) was conducted. Four SNPs (rs7574865, rs8179673, rs10181656, rs11889341) in STAT4 gene were genotyped by using polymerase chain reaction followed by denaturing high-performance liquid chromatography (PCR-DHPLC) and DNA sequencing. KEY FINDINGS: The genotype and allele distributions of four polymorphisms were significantly different in individuals with RA compared to controls, with SNP rs7574865 T allele and T/T genotype showing the most significant association with susceptibility to RA (uncorrected P=1×10(-4), OR=1.645, 95% CI=1.272-2.129; uncorrected P=4.8×10(-5), OR=3.111, 95% CI=1.777-5.447, respectively). Stratification studies showed that STAT4 gene polymorphisms were significantly associated with anti-cyclic citrullinated peptide (anti-CCP) positive subgroup in Northwestern Chinese Han population. SIGNIFICANCE: These findings strongly suggest that STAT4 genetic polymorphisms are associated with RA in Northwestern Chinese Han population, and support the hypothesis of STAT4 gene polymorphisms increasing the risk for RA across major populations.

Association of mtDNA D-loop polymorphisms with risk of gastric cancer in Chinese population.

The aim of present study was to evaluate the association of common polymorphisms detected in mitochondrial DNA (mtDNA) D-loop region (mononucleotide repetitive D310, single nucleotide polymorphism (SNP) D16521) with susceptibility to gastric cancer (GC) in northwestern Chinese population. A total of 180 GC patients and 218 healthy controls were investigated by using PCR- denaturing high performance liquid chromatography (DHPLC) assay. Genotype and allele distributions and haplotype construction were analyzed in case-control study. We found D310 and D16521 heteroplasmy were significantly different between GC cases and controls (p < 0.05), and D16521 homoplasmy showed association with histological grade of GC (p < 0.05). Haplotype 7C/T, 8C/C and 9C/C had significant association with GC risk implied from analysis of D310 and D16521. Taken together, these findings suggested that mtDNA D-Loop polymorphisms and haplotypes may contribute to genetic susceptibility to GC in Chinese population.

Fc receptor-like 3 gene polymorphisms confer susceptibility to rheumatoid arthritis in a Chinese population.

Polymorphisms in the Fc receptor-like 3 (FCRL3) gene have been reported to be associated with rheumatoid arthritis (RA) in Japanese populations. However subsequent studies have yielded conflicting results. Hence the aim of present study was to clarify whether these genetic variants in FCRL3 gene are associated with RA in a Chinese population. We conducted a case-control study of 234 RA patients and 260 controls by genotyping four polymorphisms in FCRL3. The genotype and allele distributions of four polymorphisms were significantly different in RA patients compared with controls (uncorrected p = 0.021 and p = 0.031; 0.027 and 0.008; 0.028 and 0.042; and 0.019 and 0.029, respectively). The FCRL3-169 C allele was significantly associated with rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP)-positive RA, but no association was detected for RF and anti-CCP-negative RA. Furthermore, the frequency of the -169C allele was increased disproportionately in female patients, and the resulting odds ratio for female homozygote was increased to 2.375 (uncorrected p = 0.006). Haplotype analysis showed that the most common haplotype TGGG was associated with decreased risk of RA (uncorrected p = 0.001, odds ratio = 0.656). However CACA appeared to be a risk haplotype for RA cases (uncorrected p = 0.031, odds ratio = 1.398). Taken together, these results suggest that FCRL3 polymorphisms and haplotypes may contribute to genetic susceptibility to RA in Chinese population.

Pharmacological intervention of tiferron and propolis to alleviate beryllium-induced hepatorenal toxicity.

Intervention of chelating agent tiferron (sodium-4,5-dihydroxy-1,3-benzene disulfonate; 300 mg/kg, intraperitoneal) with propolis (honey beehive product; 200 mg/kg, p.o.) was evaluated to encounter the characteristic biochemical and ultra-morphological alterations following subchronic exposure to beryllium. Female albino rats were challenged with beryllium nitrate (1 mg/kg, i.p.) daily for 28 days followed by treatment of the above-mentioned therapeutic agents either individually or in combination for five consecutive days. Exposure to beryllium increased its concentration in the serum, liver and kidney, and caused significant alterations in cytochrome P450 activity, microsomal lipid peroxidation and proteins. Activities of alkaline phosphatase, lactate dehydrogenase, gamma-glutamyl transpeptidase, bilirubin, creatinine and urea in the serum and activity of acid phosphatase, alkaline phosphatase, adenosine triphosphatase, glucose-6-phophatase and succinic dehydrogenase in the liver and kidney were significantly altered after beryllium administration. Beryllium exposure also induced severe hepatorenal alterations at histopathological and ultra-morphological level. Tiferron along with propolis dramatically reversed the alterations in all the variables more towards control rather than their individual treatment. The study concludes that pharmacological intervention of tiferron and propolis is beneficial in attenuating beryllium-induced systemic toxicity.

Evaluation of the association between retinal binding protein 4 polymorphisms and type 2 diabetes in Chinese by DHPLC.

Serum retinal binding protein 4 (RBP4) was recently described as a new liver- and adipocyte-derived signal that may contribute to Type 2 diabetes mellitus (T2DM) and insulin resistance. The aim of this study was to test whether the RBP4 gene could be used as a genetic marker to predict the development of T2DM amongst the Chinese population of Han. For this study, a normal control group of 115 healthy subjects and an experimental group of 107 patients with T2DM were examined. A combined method of denaturing high-performance liquid chromatography (DHPLC) and sequencing was applied to the detection of the RBP4 gene variants. Two SNPs, rs17484721 and rs36035572, were analyzed. Phenotypes and biochemical indicators related to the metabolism of glucose and lipid were measured. We found that there are significant differences between the control group and the patients group in terms of their respective distributions of genotype and allele frequency. The TG levels of the TT and II genotype was significantly higher than that of the TC + CC and ID + DD, respectively, in both patient group and control group. These findings suggest that the variations in the RBP4 gene may be associated with T2DM and serum triglyeride levels in the Han Chinese.

Association of sterol regulatory element-binding protein-1c gene polymorphism with type 2 diabetes mellitus, insulin resistance and blood lipid levels in Chinese population.

AIMS: The sterol regulatory element-binding protein (SREBP)-1c gene has been identified as a susceptibility gene in metabolic diseases such as type 2 diabetes mellitus (T2DM), obesity, dyslipidemia and insulin resistance. Previous studies suggest that SNP17 (rs2297508, exon18c and G952G) of SREBP-1c gene and a common SREBP-1c SNP6 (rs11868035) are associated with an increased risk of T2DM. The present study aimed to confirm the previously reported association in a Chinese population and to examine the two SREBP-1c SNPs for their associations with insulin resistance and blood lipid. METHODS: We genotyped two SREBP-1c SNPs in a case-control study (n=327) from Chinese, including 156 patients with T2DM and 171 healthy controls, using polymerase chain reaction-denaturing high-performance liquid chromatography (PCR-DHPLC) and tested for association with type 2 diabetes, insulin resistance and blood lipid, respectively. Genotype and allele distributions and haplotype construction were analysed. RESULTS: The genotype and allele distributions of rs2297508 and rs11868035 polymorphisms were significantly different in type 2 diabetic patients compared to controls (P=0.002 and P=0.013; 0.00 and 0.001, respectively). Haplotype analyses showed significant association with diabetes risk and confirmed the results of the single SNP analyses. The plasma levels of LDL-c of the minor allele-C carriers of the two SNPs were both significantly higher than the noncarriers in the control group (P<0.05). Furthermore, insulin resistance index (HOMA-IRI) of the rare homozygotes C/C of rs11868035 was significantly lower than that of T/T in the T2DM group (P<0.05). CONCLUSIONS: These findings indicate that the SREBP-1c SNPs rs2297508 and rs11868035 are associated with a significantly increased risk of T2DM and dyslipidemia in the Chinese population. Moreover, the SNP (rs11868035) is closely related to insulin resistance (IR) in diabetic patients.