Meta-analysis of MCP-1 promoter ?2518 A/G polymorphism and SLE susceptibility

The aim of this meta-analysis was to summarize results on the association of monocyte chemoattractant protein-1(MCP-1) promoter -2518 A/G polymorphism with systemic lupus erythematosus (SLE) susceptibility. We searches all the publications about the association between MCP-1 promoter -2518 A/G polymorphism and SLE from Pubmed, Elsevier Science Direct, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure. The meta-analysis was performed for genotypes AA verse GG, AA+AG verse GG, AA verse AG+GG, and A allele verse G allele in a fixed/random effect model. A total of 14 studies (2,333 cases and 2,391 controls) were included in the meta-analysis. When all groups were pooled, we had not observed significant association between A allele and G allele (OR = 0.94, 95 %CI = 0.79-1.12, P = 0.50). When analysis were restricted to more ethnically homogeneous populations, the similar results were found in European population and Asian population (OR = 1.05, 95 %CI = 0.75-1.46, P = 0.80; OR = 1.00, 95 %CI = 0.86-1.17, P = 0.99). However, we had not detected a significant association between MCP-1 promoter -2518 A/G polymorphism and SLE when examining the genotypes AA verse GG, AA+AG verse GG, AA verse AG+GG. The meta-analysis did not demonstrate the association between MCP-1 promoter -2518 A/G polymorphism and SLE.     

Genetic polymorphisms of the interleukin-18 gene and risk of prostate cancer

Genetic factors are known to be important in the development of prostate cancer. Interleukin-18 (IL-18) is a multifunctional cytokine that induces interferon-gamma secretion and plays an important role in antitumor immunity. Variations in the DNA sequence in the IL-18 gene promoter may lead to altered IL-18 production and/or activity, and so this can modulate an individual's susceptibility to prostate cancer. To test this hypothesis, we investigated the relationship of IL-18 gene promoter -137 G/C and -607 C/A polymorphisms and their haplotypes with the risk of prostate cancer. We analyzed two single nucleotide polymorphisms of IL-18 gene promoter -137 G/C and -607 C/A in 265 patients with prostate cancer and 280 age- and sex-matched controls, using sequence-specific primers-polymerase chain reaction strategy. There were significant differences in the genotype and allele distribution of -137 G/C polymorphism of the IL-18 gene among cases and controls. The -137 GC and CC genotypes were associated with a significantly increased risk of prostate cancer as compared with the -137 GG genotypes [odds ratio (OR) = 1.721; 95% confidence interval (CI): 1.187-2.496; p = 0.004, and OR = 2.181; 95% CI: 1.034-4.603; p = 0.037, for GC and CC, respectively]. Consistent with the results of the genotyping analyses, the -137C/-607A haplotype was associated with a significantly increased risk of prostate cancer as compared with the -137G/-607C haplotype (OR = 1.544; 95% CI, 1.137-2.096; p = 0.005). This study shows for the first time an association between IL-18 gene promoter -137 G/C polymorphism and prostate cancer in a Chinese population.     

Office blood pressure,heart rate and A(-596)G interleukin-6 gene polymorphism in apparently healthy Czech middle-aged population

The aim of the study was to assess the association between promoter polymorphism [A(-596)G] in interleukin-6 gene and office systolic and diastolic blood pressures, and the heart rate (HR) in apparently healthy Czech subjects. Furthermore, we evaluated the possible influence of gender, BMI and smoking on these supposed associations. An age-matched (40-50 years) and gender-matched (F/M=81/89) sample of apparently healthy Czech subjects (n=170, F/M=81/89) without hypertension, other cardiovascular diseases or diabetes was examined. The A(-596)G Il-6 gene polymorphism was detected by the PCR method. No differences in genotype distribution and/or allelic frequency was found between groups with lower systolic blood pressure (? 122 mm Hg) and higher systolic blood pressure (> 122 mm Hg). Similarly, no differences in the IL-6 polymorphism were found between lower (? 86 mm Hg) and higher (> 86 mm Hg) diastolic blood pressure groups. However, we proved a significant increase of genotypes AG+GG as well as the allele (-596)G in higher (>78 beats/min) heart rate group. The genotypes AG+GG represent significantly higher relative risk for higher HR frequency, especially in women. Among lean persons with a low heart rate frequency, fewer AG+GG genotypes were determined than among any other subjects. The genotypes AG+GG are more frequent in non-smoking persons with higher HR compared to non-smoking subjects with lower HR, especially in women. Gender, BMI and smoking substantially modify the distribution of A(-596)G Il-6 gene polymorphism in apparently healthy persons with lower or higher heart rate.     

Functional polymorphisms of cyclooxygenase-2 gene and risk for hepatocellular carcinoma

Cyclooxygenase-2 (COX-2) influences carcinogenesis through immune response suppression, apoptosis inhibition, regulation of angiogenesis and tumor cell invasion, and metastasis. It is now well established that COX-2 is overexpressed in many premalignant, malignant, and metastatic cancers, including hepatocellular carcinoma (HCC). DNA sequence variations in the COX-2 gene may lead to altered COX-2 production and/or activity, and so they cause inter-individual differences in the susceptibility to HCC. Functional coding region polymorphisms -1195A>G (rs689466), -765G>C (rs20417), and +8473T>C (rs5275) in the COX-2 gene have recently been shown to be associated with several human cancers but their association with HCC has yet to be investigated. We used hospital-based case-control study to assess the hypothesis that the functional COX-2 variation may affect individual susceptibility to the HCC. COX-2 polymorphisms were investigated in 129 confirmed subjects with HCC and 129 cancer-free control subjects matched on age, gender, smoking, and alcohol consumption using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. The distribution of the COX-2 -1195A>G and +8473T>C genotypes were not significantly different between HCC cases and control. However, proportion of the COX-2 -765CC genotype which leads to a 30% reduction of the COX-2 promoter activity was significantly lower in patients with HCC (3.1%) when compared to control subjects (11.6%) (P < 0.05). Logistic regression analyses revealed that the COX-2 -765G>C variant genotype (-765CC) was associated with a significantly decreased risk of HCC compared with the -765GG wild-type homozygotes [P < 0.05, odds ratio (OR) = 0.25, 95% confidence interval (CI) = 0.08-0.79]. Our results suggest for the first time that the -765CC genotype of COX-2 -765G>C polymorphism, causing lower COX-2 gen expression, is a genetic protective factor for HCC. However, because this is the first report concerning the COX-2 -1195A>G, -765G>C, and +8473T>C polymorphisms and the risk of HCC, independent studies are needed to validate our findings.     

Association of the IL-6 -174G/C gene polymorphism with knee osteoarthritis in a Thai population

Osteoarthritis is a chronic progressive degenerative joint disease characterized by age-related regressive change in articular cartilage. A single nucleotide polymorphism has been described at position -174 of the interleukin-6 (IL-6) promoter region, leading to three possible genotypes, GG, GC, and CC. We investigated a possible association of the IL-6 -174G/C gene polymorphism with knee osteoarthritis in a Thai population. Genotype distributions and allelic frequencies of the IL-6 -174G/C polymorphism were investigated in 115 knee osteoarthritis patients and 100 healthy controls. Genotyping was performed using PCR-RFLP. The genotype distribution of IL-6 was 79 GG, 36 GC, 0 CC in knee osteoarthritis patients and 88 GG, 12 GC, 0 CC in controls. The frequency of the GC genotype in subjects with knee osteoarthritis was higher than in controls (P< 0.001). Logistic regression analysis showed that the GC genotype was independently associated with increased risk of knee osteoarthritis (odds ratio = 3.3, 95% confidence interval = 1.6-6.9, P = 0.001). These findings suggest that the -174G/C polymorphism of the IL-6 gene promoter plays a role in the pathogenesis of knee osteoarthritis.     

Genetic variation in the NBS1 gene is associated with hepatic cancer risk in a Chinese population

NBS1 plays important roles in maintaining genomic stability as a key DNA repair protein in the homologous recombination repair pathway and as a signal modifier in the intra-S phase checkpoint. We hypothesized that polymorphisms of NBS1 are associated with hepatic cancer (HCC) risk. The NBS1 rs1805794 C/G polymorphism has been frequently studied in some cancers with discordant results, but its association with HCC has not been investigated. Moreover, studies of the 3'UTR variant rs2735383 have not touched upon HCC. This study examined the contribution of these two polymorphisms to the risk of developing HCC in a Chinese population. NBS1 genotypes were determined in 865 HCC patients and 900 controls and the associations with risk of HCC were estimated by logistic regression. Compared with the rs1805794 GG genotype, the GC genotype had a significantly increased risk of HCC (adjusted odds ratios [OR]=1.41; 95% confidence interval [CI]=1.11-1.80), the CC carriers had a further increased risk of HCC (OR=2.27; 95% CI=1.68-3.14), and there was a trend for an allele dose effect on risk of HCC (p<0.001). Also, we found that the risk effect of rs1805794 CC+CG was more pronounced in HCC patients that drank (OR=2.28, 95% CI=1.55-3.29 for drinkers; OR=1.31, 95% CI=1.00-1.77 for nondrinkers). However, there was no significant difference in genotype frequencies of rs2735383 G/C site between cases and controls. These findings suggest that rs1805794 C/G polymorphism in NBS1 may be a genetic modifier for developing HCC.     

Il6 gene promoter polymorphism (-174G/C) influences the association between fat mass and cardiovascular risk factors

During the last decades, the prevalence of obesity has increased rapidly among young people. A polymorphism in the promoter region of the IL6 gene (-174G/C), has been previously reported to be involved in obesity and metabolic syndrome development. Therefore, the aim of the study was to examine whether the IL6-174G/C polymorphism influence the association of body fat with low-grade inflammatory markers and blood lipids and lipoproteins in Spanish adolescents. 504 Spanish adolescents participating in the AVENA study were genotyped for the-174G/C polymorphism of the IL6 gene. Anthropometric and body composition measurements were taken and blood samples were collected for plasma molecules determinations. No differences between genotypes were observed in anthropometric values, body composition measurements and plasma markers concentration. Physical activity level differ between genotypes with subjects carrying the C allele of the polymorphism being significantly (p<0.05) more active than GG subjects. The association between body fat mass and plasma glucose was influenced by the -174G/C polymorphism of the IL6 gene. Subjects carrying the C allele of the mutation seem to have higher values of lipoprotein (a) and C-reactive protein as their percentage of body fat mass increase. Our results suggest that this promoter polymorphism influences the association between adiposity and some plasma markers.     

The MHC2TA -168A>G gene polymorphism is not associated with rheumatoid arthritis in Austrian patients

An association between susceptibility to rheumatoid arthritis (RA) and a common -168A>G polymorphism in the MHC2TA gene with differential major histocompatibility complex (MHC) II molecule expression was recently reported in a Swedish population. The objective of the present study was to replicate this finding by examining the -168A>G polymorphism in an Austrian case-control study. Three hundred and sixty-two unrelated RA cases and 351 sex-matched and age-matched controls as well as 1,709 Austrian healthy individuals were genotyped. All participants were from the same ethnic background. Genotyping was performed using 5' allelic discrimination assays. The association between susceptibility to RA and the -168A>G single nucleotide polymorphism was examined by chi-square test. Comparison was made assuming a dominant effect (AG + GG genotypes versus AA genotype). In contrast to the primary report, the frequency of MHC2TA -168G allele carriers was not significantly different between patients and controls in the Austrian cohort. The homozygous MHC2TA -168 GG genotype was more frequent in matched controls than in Austrian RA patients. There was no association between the presence of RA-specific autoantibodies and the MHC2TA -168 GG genotype. In this cohort of Austrian patients, no association between the MHC2TA polymorphism and RA was found.     

PSA and androgen-related gene (AR, CYP17, and CYP19) polymorphisms and the risk of adenocarcinoma at prostate biopsy

The aim of the present study was to examine the impact of polymorphisms in prostate-specific antigen (PSA) and androgen-related genes (AR, CYP17, and CYP19) on prostate cancer (PCa) risk in selected high-risk patients who underwent prostate biopsy. Blood samples and prostate tissues were obtained for DNA analysis. Single-nucleotide polymorphisms in the 50-untranslated regions (UTRs) of the PSA (substitution A>G at position-158) and CYP17 (substitution T>C at 50-UTR) genes were detected by polymerase chain reaction (PCR)-restriction fragment length polymorphism assays. The CAG and TTTA repeats in the AR and CYP19 genes, respectively, were genotyped by PCR-based GeneScan analysis. Patients with the GG genotype of the PSA gene had a higher risk of PCa than those with the AG or AA genotype (OR=3.79, p=0.00138). The AA genotype was associated with lower PSA levels (6.44 +/- 1.64 ng=mL) compared with genotypes having at least one G allele (10.44 +/- 10.06 ng=mL) ( p=0.0687, 95% CI=0.3146 to 8.315, unpaired t-test). The multivariate analysis confirmed the association between PSA levels and PSA genotypes (AA vs. AG+ GG; chi2=0.0482) and CYP19 (short alleles homozygous vs. at least one long allele; chi2=0.0110) genotypes. Genetic instability at the AR locus leading to somatic mosaicism was detected in one PCa patient by comparing the length of AR CAG repeats in matched peripheral blood and prostate biopsy cores. Taken together, these findings suggest that the PSA genotype should be a clinically relevant biomarker to predict the PCa risk.     

Association between VHL single nucleotide polymorphism (rs779805) and the susceptibility to prostate cancer in Chinese

The Von Hippel-Lindau (VHL) tumor suppressor gene is a crucial regulator of the hypoxia response pathway and plays an important role in tumorigenesis, particularly in tumor growth and vascularization. We hypothesize that polymorphisms in the functional region of VHL may influence susceptibility to prostate cancer (PCa). We genotyped a potentially functional polymorphism (rs779805) in 5' UTR region of VHL in a case-control study of 665 PCa patients and 715 cancer-free controls in a Chinese population using the Taqman assay. The genetic associations between the incidence and progression of PCa were assessed by logistic regression. We observed that the rs779805 A>G polymorphism was significantly associated with risk for PCa. Compared with the AA genotype, the AG and AG/GG genotypes were associated with decreased risk of PCa (adjusted odds ratio [OR]=0.79, 95% confidence interval [CI]=0.62-0.99, and adjusted OR=0.76, 95% CI=0.61-0.95, respectively). Further, this decreased risk was more pronounced in the subgroups of nonsmokers (OR=0.73, 95% CI=0.54-0.98), nondrinkers (OR=0.70, 95% CI=0.54-0.91) and patients without family history of cancer (OR=0.72, 95% CI=0.57-0.92). In addition, the decreased risk associated with rs779805 variant genotypes (AG/GG) was more pronounced among the prostate specific antigen (PSA)>20 ng/mL subgroup (OR=0.68, 95% CI=0.49-0.95). Our findings suggest that the rs779805 A>G polymorphism in VHL may confer susceptibility to PCa in the Chinese population.     

MDM2 promoter polymorphism is associated with increased susceptibility to hepatocellular carcinoma in Turkish population

Background: The mouse double minute 2 (MDM2) gene represents one of the central nodes in the p53 pathway. A naturally occurring T/G single nucleotide polymorphism (SNP) in the intronic promoter of MDM2, SNP309 (rs2279744), was shown to influence MDM2 expression and p53 activity. SNP in the promoter region of MDM2 gene has recently been shown to be associated with accelerated tumor formation in both hereditary and sporadic cancers in humans. In this study, we aim to evaluate the association of SNP309 with the risk of hepatocellular carcinoma (HCC) development among Turkish population. Methods: MDM2 SNP309 polymorphism was investigated in 110 confirmed subjects with HCC and 110 cancer-free control subjects matched on age, gender, smoking and alcohol consumption by using a polymerase chain reaction-restriction fragment length polymorphism assay. Results: The allele frequencies of case subjects (T, 0.48; G, 0.52) were significantly different from those of control subjects (T, 0.65; G, 0.35) (p = 0.003). The proportion of GG genotype of the SNP309 in patients with HCC (26%) was significantly higher than that in patients without HCC (14%). We observed that compared with the TT genotype, the genotypes containing G allele [TG (OR, 2.19; 95% CI, 1.18–4.07; p = 0.013) or GG (OR, 3.63; 95% CI, 1.65–8.00; p = 0.001)] were associated with significant increased susceptibility to HCC. Conclusion: Our findings suggest that the MDM2 promoter SNP309 G allele is associated with presence of HCC in Turkish population.     

Functional rs6265 polymorphism in the brain-derived neurotrophic factor gene confers protection against neurocognitive dysfunction in posttraumatic stress disorder among Chinese patients with hepatocellular carcinoma

Posttraumatic stress disorder (PTSD) is a psychiatric disorder that plagues trauma survivors. Evidence shows that brain-derived neurotrophic factor (BDNF) may be involved in the occurrence and development of PTSD. Here we tried to demonstrate whether BDNF gene polymorphisms are correlated with neurocognitive function following PTSD in patients with hepatocellular carcinoma (HCC). This study included 102 patients with HCC complicated with PTSD, 146 HCC patients, and 152 healthy volunteers. Initially, we evaluated the neurocognitive function of the study subjects. Next, we measured BDNF G11757C and rs6265 polymorphisms by polymerase chain reaction-restriction fragment length polymorphism. The correlation of BDNF polymorphisms and BDNF level with HCC complicated with PTSD was evaluated. The results revealed that HCC complicated with PTSD showed decreased serum BDNF level and Mini-mental state examination (MMSE) score. Serum BDNF level of HCC and HCC complicated with PTSD was positively correlated with MMSE score. GA + AA allele and A allele of rs6265 increased the risk of PTSD among patients with HCC. GA and AA genotypes of rs6265 were correlated with the decreased MMSE score of HCC complicated with PTSD. Haplotype GA of rs6265 and G11757C increased the risk of PTSD for HCC, while haplotype CG decreased this risk. Lastly, the logistic regression analysis suggested that low BDNF level was a contributor to HCC complicated with PTSD, while GG genotype of rs6265 served as a protective factor. Collectively, this study defines the GG genotype of BDNF rs6265 polymorphism as a protector to HCC complicated with PTSD. In addition, these results provided a promising target for PTSD prevention in patients with HCC.     

Association of leptin genetic polymorphism -2548 G/A with gestational diabetes mellitus

The aim of this study was to investigate possible associations of -2548 G/A polymorphism in leptin gene promoter and pregnancy-associated diseases with abnormal fetal growth such as preeclampsia and gestational diabetes. The study was also focused on whether it is rather maternal or fetal variants that determines the pathological growth status. Peripheral or cord blood samples obtained from 49 preeclamptic women and their 39 newborns, 53 healthy controls and their 53 healthy newborns and 48 patients with gestational diabetes mellitus were evaluated for leptin gene (LEP) locus -2548 genotypes. The significantly higher risk for gestational diabetes mellitus was observed in the presence of an allele (AA and AG genotypes) against carriers of GGgenotype(OR=2.84, 95%CI1.14-7.07,p=0.02). Thereisa significant risk of diabetes mellitus associated to A allele (OR=1.79, 95%CI 1.02-3.14, p=0.03). Furthermore, evaluations of preeclamptic patients' data revealed a significant association of genotype distribution and delivery and spontaneous abortion rate, where the GG carriers performed the highest pregnancy rate while the AG carriers performed the lowest spontaneous abortion rate. Our results support the hypothesis for -2548 G/A leptin gene polymorphism involvement in ethiopathogenesis of pregnancy-associated diseases with abnormal fetal growth, especially gestational diabetes mellitus.     

The genetic association between osteoprotegerin gene polymorphisms and fracture risk in Chinese Han population

This article put the genetic association exploration of osteoprotegerin (OPG) gene polymorphisms in promoter region (A-163G, T-245G) and fracture risk first and hoped to explain the ethology of fracture. The genotyping of OPG gene polymorphisms was conducted with the method of polymerase chain reaction-restriction fragment length polymorphism in 125 fracture patients and 138 relative controls. The genotype frequencies of selected controls based on OPG gene polymorphisms were checked by the χ² test whether conformed to Hardy–Weinberg equilibrium (HWE). The relative risk was represented with odds ratio (OR) and 95% confidence interval (95% CI) between gene polymorphism and disease. The linkage disequilibrium (LD) and haplotype were also analyzed. The genotypes distributions of selected controls in OPG polymorphisms conformed to HWE. The G allele of A-163G polymorphism carriers had the tendency to suffer from fracture in the same condition, compared with A allele carriers (OR = 1.63, 95% CI = 1.04–2.55). TG and TG/GG genotypes of OPG T-245G polymorphism also showed the increased risk of fracture development, but not TT genotype (OR = 2.22, 95% CI = 1.15–4.28; OR = 2.45, 95% CI = 1.28–4.68). Likely, the mutant allele G had an abnormally higher frequency in cases than controls (14.00% and 6.16%). These two polymorphisms existed the LD and the haplotype G _-163–G _-245 obviously increased the risk of fracture. OPG A-163G, T-245G polymorphisms were associated with the onset of fracture and both the independent risk factors.     

IL-6 -174G/C polymorphism and IL-6 serum levels in patients with liver cirrhosis and hepatocellular carcinoma

Recently, a link between high levels of circulating IL-6 and hepatocellular carcinoma (HCC) has been proposed. In addition, single nucleotide polymorphisms (SNPs) in the promoter region of the IL-6 gene have been reported to be related to several inflammatory-related conditions, including cancer. The purpose of this article is: (1) to evaluate the frequencies of SNPs in the IL-6 promoter region at position -174 and IL-6 serum levels in a group of patients with HCC and underlying liver cirrhosis (LC), and compare them with a group of LC patients without HCC; (2) to determine whether a possible correlation exists between the allelic variations, IL-6 serum levels, and the risk of developing HCC. The study included 105 HCC and 95 LC patients. Genomic DNA was isolated using commercially available kits. DNA samples were typed for relevant SNPs of the IL-6 promoter region (-174?G>C, G allele being associated with higher levels of the cytokine). The Restriction Fragment Length Polymorphism (RFLP-PCR) method was used to type the SNPs. IL-6 serum levels were determined using an ultrasensitive commercially available ELISA kit. IL-6 serum levels were higher in G/G compared to C/C genotypes only in HCC (z=2; p=0.04) and G/G versus G/C (z=1.8; p<0.03). IL-6 serum levels in G carriers (G/G+G/C) were higher in HCC 4.8 (0.2-17.5) versus LC patients 2.2 (0.07-11.5) (z=2.8; p=0.004). There was no difference for genotype C/C. IL-6 serum levels in HCC correlated with G carriers (G/G+G/C) (ρ=0.25, p=0.05). A positive correlation was also found between sIL-6 levels and some parameters of liver function both in LC and in HCC patients.     

The association between proinflammatory cytokine polymorphisms and cerebral palsy in very preterm infants

Cerebral palsy (CP) is a nonprogressive motor disorder caused by white matter damage in the developing brain and is often accompanied with cognitive and sensory disabilities. The risk of CP is higher among infants born preterm than in more mature infants. Intrauterine infection/inflammation, activation of the cytokine network and elevated levels of proinflammatory cytokines in neonatal blood or in amniotic fluid to which the preterm infant is exposed, has been identified as the most common cause of preterm delivery, periventricular leukomalacia (PVL) and CP. The aim of our study was to evaluate the possible association of four TNFα promoter single nucleotide polymorphisms (SNPs) (-1031 T/C, -857 C/T, -308 G/A and -238 G/A), two IL1β SNPs (-511 C/T and +3954 C/T) and one IL6 (-174 C/G) polymorphism with susceptibility to CP in very preterm infants. Statistically significant association between TNFα -1031 T/C high expression genotypes (TC and CC) (OR, 2.339; p=0.016) as well as between TNFα -1031 C high expression allele (OR, 2.065; p=0.013) and risk of CP was observed. In addition, statistically significant association was found between TNFα TC, CC, GG, GG -1031/-857/-308/-238 genotypes combination (OR, 3.286; p=0.034) and risk of CP. Statistically significant association between IL1β TT, CC -511/+3954 genotypes combination and risk of CP (OR, 4.000; p=0.027) was also found. In CP patients with cystic PVL (cPVL) statistically significant association was found between TNFα -1031 T/C high expression genotypes (TC and CC) (OR, 2.361; p=0.038), IL1β -511 C/T high expression genotype TT (OR, 3.215; p=0.030) as well as IL1β -511 T high expression allele (OR, 1.956; p=0.019) and risk of CP. Statistically significant association was also found in patients with cPVL between TNFα TC, CC, GG, GG -1031/-857/-308/-238 genotypes combination (OR, 4.107; p=0.024), as well as IL1β TT, CC -511/+3954 genotypes combination (OR, 7.333; p=0.005) and risk of CP. Our results suggest the role of TNFα and IL1β polymorphisms which have previously been associated with higher circulating levels of these cytokines in genetic susceptibility to white matter damage and consequently CP in very preterm infants.     

Association of the -112A>C polymorphism of the uncoupling protein 1 gene with insulin resistance in Japanese individuals with type 2 diabetes

The -112A>C polymorphism (rs10011540) of the gene for uncoupling protein 1 (UCP1) has been associated with type 2 diabetes mellitus in Japanese individuals. The aim of the present study was to investigate the effects of this polymorphism, as well as the well-known -3826A>G polymorphism (rs1800592), on clinical characteristics of type 2 diabetes. We determined the genotypes of the two polymorphisms in 93 Japanese patients with type 2 diabetes. Intramyocellular lipid content and hepatic lipid content (HLC) were measured by magnetic resonance spectroscopy. No significant differences in age, sex, BMI, or HbA1c level were detected between type 2 diabetic patients with the -112C allele and those without it. However, homeostasis model assessment for insulin resistance (p=0.0089) and HLC (p=0.012) was significantly greater in patients with the -112C allele. We did not detect an association of the -3826A>G polymorphism (rs1800592) of UCP1 gene with any measured parameters. These results suggest that insulin resistance caused by the -112C allele influences the susceptibility to type 2 diabetes.     

绝经后女性CYP19基因Val80及OPG基因A163G多态性与骨密度的相关性研究

探讨细胞色素P450 19 (CYP19) 基因Val80多态性及护骨素(OPG) 基因A163G多态性与绝经后女性骨密度 (BMD) 的关系。随机选择居住在重庆的绝经后女性200例, 采用多聚酶链反应-限制性片段长度多态性法检测Val80及A163G多态性, 采用Norland公司XR-46系列双能X线骨密度仪测量股骨近端及腰椎BMD。 200名绝经后女性中Val80基因型GG、GA及AA的频率分别为19.5％、44.5％及36.0％; A163G基因型GG、GC 及CC的频率分别为: 13.0％, 42.0％及45.0％; 基因型频率分布均符合Hardy-Weinberg平衡 (P＞0.05)。协方差分析及多元逐步回归分析显示CYP19基因第3外显子Val80多态性与绝经后女性BMD无相关性 (P＞0.05)。除大转子外, A163G位点AG/GG/AG+GG基因型者股骨颈、Ward’s三角及腰椎BMD均较AA基因型者低, A163G基因型与股骨颈、Ward’s三角及腰椎BMD有相关性 (P＜0.05)。OPG基因启动子区A163G多态性分布存在明显的种族差异, 且与绝经后女性BMD有一定关联, AA型对BMD具有一定的保护作用, G等位基因是BMD降低的危险因素。