脂联素基因SNP+45 T/G单核苷酸多态性与冠心病的相关性研究

目的:研究中国华南地区汉族人脂联素基因SNP+45T/G单核苷酸多态性与冠心病的相关性。方法:以153例冠脉造影证实为冠心病的非糖尿病患者为冠心病组,以73例健康者为对照组,采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法分析脂联素基因SNP+45T/G单核苷酸多态性与冠心病的相关性,ELISA法测定血浆脂联素水平。结果:冠心病组T/G+G/G型频率、G等位基因频率均高于对照组(P0.05)。Logistic回归分析发现脂联素基因SNP+45 T/G+G/G型与冠心病正相关(OR:2.132,95.0%C I:1.034-4.397,P0.05),血浆脂联素水平与冠心病的发病呈负相关(OR:0.868,95.0%C I:0.785-0.959,P0.05)。结论:脂联素基因SNP+45 T/G+G/G型可能是华南地区汉族人冠心病的易感基因型。     

成都地区汉族人群PPARGC1A基因Thr394Thr位点G/A多态性与2型糖尿病及胰岛素抵抗的相关性研究

目的 了解中国成都地区汉族人群过氧化物酶体增殖物激活受体γ辅助激活因子-1α基因(peroxisome proliferator-activated receptor gamma,coactivator 1 alpha,PPARGC1A;又名PGC-1α)Thr394Thr位核苷酸G/A的基因型分布,探讨该多态性与2型糖尿病(type 2 diabetes mellitus,T2DM)、胰岛素抵抗及其他代谢异常的关系.方法 应用聚合酶链反应-限制性片段长度多态性技术检测151例无亲缘关系的T2DM患者和156名糖耐量正常对照者PPARGC1A基因Thr394Thr位核苷酸G/A多态性.所有研究对象均测定血糖、胰岛素、血脂,测量身高、体重、腰围、血压.结果 与正常对照组相比,T2DM组的体重指数、腰围、血压、甘油三酯水平均显著增高(P＜0.05),而高密度脂蛋白胆固醇(high density lipoprotein-cholesterol,HDL-C)水平显著降低(P＜0.05).A等位基因的频率在T2DM及正常对照组分别为22.5%、18.6%,AG基因型频率在两组分别为43.7%、37.2%,差异无统计学意义.在T2DM组中,AA+AG基因型的空腹胰岛素、稳态模型评估法胰岛素抵抗指数(homeostasis model aseessment-insulin resistance,HOMA-IR)及腰围明显高于GG基因型,HDL-C显著低于GG基因型(P＜0.05).无论T2DM和正常对照,A等位基因携带者HOMA-IR明显高于GG者.结论 PPARGC1A基因Thr394Thr位核苷酸G/A多态性与胰岛素抵抗存在明显相关,并可能与T2DM患者中心性肥胖及低HDL-C水平相关,其与T2DM发病的关系有待进一步研究.     

Association of the human adiponectin gene and insulin resistance

Adiponectin is an adipocyte-secreted protein that modulates insulin sensitivity and whose low circulating concentration is associated with insulin resistance. In the present study, we analysed the association between two single-nucleotide polymorphisms (SNPs) in the adiponectin gene and insulin resistance in 253 nondiabetic subjects. In addition, we investigated whether this association is modulated by body mass index (BMI) levels. The SNPs +45T>G and +276G>T in the human adiponectin gene were detected in real-time PCR with LightCycler. No association was found with the +45T>G SNP. The +276G>T SNP was associated with higher BMI (P<0.01), plasma insulin (P<0.02) and HOMA(IR) (P<0.02). To analyse the possible interaction between BMI and the adiponectin gene on insulin resistance, the study group was divided into two subgroups, according to the BMI below or above the median of 26.2 kg/m(2). In both subgroups, subjects carrying the +276G>T SNP had higher HOMA(IR); however, the difference was highly significant among leaner (P<0.001), but not among heavier individuals, indicating that BMI status and the adiponectin gene interact in modulating insulin resistance. Among individuals with BMI <26.2 kg/m(2), the relative risk of insulin resistance was 9.7 (CI: 1.32-87.7, P<0.035). In a subgroup of 67 subjects, carriers of the +276G>T SNP had significantly (P<0.05) lower mean serum adiponectin levels (25.7 ng/ml) compared to noncarriers (37.0 ng/ml), suggesting a possible influence of the +276G>T SNP on adiponectin levels. In summary, we observed an association between the +276G>T SNP in the adiponectin gene and insulin resistance. In particular, among leaner individuals, the adiponectin gene appears to determine an increased risk to develop insulin resistance.     

Association of the T45G polymorphism in exon 2 of the adiponectin gene with polycystic ovary syndrome: role of Delta4-androstenedione

BACKGROUND: Insulin resistance is a prominent feature of polycystic ovary syndrome (PCOS), independent of obesity. It is possible that insulin resistance in PCOS is genetically determined. Adiponectin is a protein that modulates insulin action and is regarded as a possible link between adiposity and insulin resistance. The objective of this study was to examine the role of the adiponectin gene T45G polymorphism, located in exon 2, in PCOS, since this polymorphism has been shown to be associated with obesity and insulin resistance. SUBJECTS AND METHODS: Two hundred and thirty-two women were studied, and were classified as follows: 132 women with PCOS [62 with body mass index (BMI) > 25 kg/m2 and 70 with BMI < 25 kg/m2] and 100 ovulating women without hyperandrogenemia (controls: 19 with BMI > 25 kg/m2 and 81 with BMI < 25 kg/m2). From all subjects a whole-blood sample was taken and was used for isolation of peripheral blood leukocytes. The adiponectin T45G polymorphism, located in exon 2, was genotyped by amplification of genomic DNA. In all subjects, serum gonadotropin, androgen, 17-OH-progesterone, fasting glucose, insulin and adiponectin levels were measured between the third and sixth day of the menstrual cycle. RESULTS: A statistically significant difference was observed in the frequency of GG and TG genotypes between women with PCOS (40/132; 30.3%) and controls (19/100; 19.0%). In a subgroup of PCOS women with high Delta4-androstenedione levels (Delta4A > 3.11 ng/ml), a statistically significant difference between the frequencies of the genotypes was also noticed compared with the control group, in contrast to the subgroup with relatively low Delta4-androstenedione levels (Delta4A < 3.11 ng/ml). No significant associations were found between this adiponectin polymorphism and BMI, testosterone level, adiponectin levels and glucose-to-insulin ratio. CONCLUSIONS: Our study suggests that adiponectin polymorphisms are not causatively involved in the metabolic disturbances of PCOS, but that an interaction between adiponectin and steroid synthesis or action might exist.     

Effects of uncoupling protein 1 and beta3-adrenergic receptor gene polymorphisms on body size and serum lipid concentrations in Japanese women

OBJECTIVES: To investigate whether the -3826 A-G point mutation of the uncoupling protein 1 (UCP1) gene and the Trp64Arg mutation of the beta3-adrenergic receptor (beta3-AR) gene are associated with increased susceptibility to weight gain and hyperlipidemia in postmenopausal women. METHODS: We genotyped 312 Japanese women for UCP1 and beta3-AR gene polymorphisms, and investigated their effects on anthropometrical parameters, serum lipid concentrations, and their changes after 4 years. RESULTS: Although body mass index (BMI), serum triglyceride, total cholesterol, and low-density lipoprotein levels were significantly higher and high-density lipoprotein levels significantly lower in postmenopausal (n=182) than in premenopausal (n=99) women, there was no significant difference in these parameters between carriers and non-carriers of the G allele in the postmenopausal women. In the premenopausal women, BMI and the 4-year change in body weight (BW) of carriers of the G allele were significantly higher than those of non-carriers of the G allele (P=0.022 and 0.048, respectively). In the postmenopausal women, the 4-year change in the level of serum triglyceride of carriers of the G allele was significantly higher (P=0.049), and the change of high-density lipoprotein was significantly lower (P=0.020) than those of non-carriers of the G allele. The beta3-AR polymorphism showed no apparent affect on these parameters. CONCLUSIONS: The -3826 A-G polymorphism of the UCP1 gene is associated with an increase in BW of premenopausal women and with the 4-year changes in serum triglyceride and high-density lipoprotein levels in postmenopausal women.     

Apolipoprotein E gene promoter (–219G/T) polymorphism is associated with premature coronary heart disease

The relationship of two apolipoprotein (apo) E gene polymorphisms and coronary heart disease (CHD) was investigated in 118 Finnish families with premature CHD and in 110 healthy control subjects. Affected siblings and probands with premature CHD had higher frequencies of the T allele of the -219G/T promoter polymorphism and the epsilon 4 allele (genotypes epsilon 4/3 or epsilon 4/4) of the apo epsilon 2/epsilon 3/ epsilon 4 polymorphism than those of healthy control subjects. Additionally, when the two apo E gene polymorphisms were combined, affected siblings and probands had a higher frequency of the -219T allele and the epsilon 4 allele combinations than did healthy controls. The -219T and the epsilon 4 alleles both separately and together were associated with higher levels of 2-h glucose in an oral glucose tolerance test. These results indicate that the two polymorphisms of the apo E gene have similar effects on the risk of coronary atherosclerosis in families with premature CHD. This risk was not explained by the effect of apo E gene polymorphisms on cholesterol metabolism, but their effect on cardiovascular risk factor clustering with insulin resistance may be of importance. We conclude that in addition to the epsilon 4 allele, also the -219G/T promoter polymorphism of the apo E gene is associated with early onset CHD.     

The C766T low-density lipoprotein receptor related protein polymorphism and coronary artery disease, plasma lipoproteins, and longevity in the Czech population

Low-density lipoprotein receptor related protein (LRP) is a multifunctional endocytic receptor involved in various biological processes including the regulation of the coagulation-fibrinolysis balance, the lipoprotein metabolism, and cellular migration, all of which relate to the development of atherosclerosis. Polymorphisms affecting the function or expression of LRP may thus influence the individual risk of atherosclerosis development. This study investigated the association between the C766T LRP polymorphism, coronary artery disease (CAD), and plasma lipoprotein levels in a large sample of Caucasian subjects of Czech nationality. In addition, the 4G/5G promoter polymorphism of the gene coding for plasminogen activator inhibitor 1 (PAI-1), the known ligand of LRP with strong antifibrinolytic potential, was ascertained to investigate its possible association with CAD. Both polymorphisms were studied using polymerase chain reaction analysis in 654 patients with angiographically confirmed CAD and in 525 controls. No statistically significant differences in allele frequencies of the polymorphisms studied were detected between patients and controls, even when men, women, hypertonic, and type II diabetic subjects were compared separately. However, the frequency of the T allele of the LRP polymorphism was significantly higher in patients than controls when only subjects with the 5G/5G PAI-1 genotype were analyzed. In addition, the T LRP allele frequency was significantly lower in subjects aged 60 years or over than in those who were younger in both groups. No significant association was observed between the LRP or PAI-1 polymorphisms and plasma lipoprotein levels in the CAD patients. Our results demonstrate that the T allele of the C766T LRP polymorphism is negatively related to longevity, and that it increases the risk of CAD development in subjects with the 5G/5G PAI-1 genotype.     

AMPKα2基因多态性与2型糖尿病及脂联素、抵抗素的关系

目的 研究甘肃地区汉族人群AMPKα2基因多态性与T2DM、胰岛素抵抗及血清脂联素、抵抗素水平的关系.方法 选取T2DM患者188例和非糖尿病正常人群179例,用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)法,检测AMPK-rs2796516G/A基因型.用酶联免疫法(ELISA)测定血清脂联素、抵抗素浓度,...     

Common polymorphisms (single-nucleotide polymorphisms SNP+45 and SNP+276) of the adiponectin gene regulate serum adiponectin concentrations and blood pressure in young Finnish men

Epidemiologic studies have shown that serum level of adiponectin, a circulating protein secreted by adipocytes, predicts the risk of type 2 diabetes and cardiovascular events. Two single-nucleotide polymorphisms (SNPs) at the adiponectin locus (T45G or G276T) of the adiponectin gene (APM1) have been associated with insulin resistance, low serum adiponectin levels, and diabetes. In the present study, the association of these polymorphisms with serum adiponectin level and insulin resistance-associated risk factors was investigated. To this aim, SNP+45 and SNP+276 of APM1 were genotyped in 252 young Finnish men. Serum adiponectin level (p < 0.001) and diastolic blood pressure (p = 0.031) were significantly higher in subjects with the T276T genotype of APM1 compared to those with the G276T or G276G genotypes. Mean diastolic blood pressure among the T276T subjects was 80 mmHg and that in subjects with the G276G and G276T genotypes below 75 mmHg. An interaction between triglycerides, diastolic blood pressure, quantitative insulin sensitivity check index, and SNP276 with regard to serum adiponectin level was found. After adjustment for other covariates, the interaction between triglycerides and SNP276 remained statistically significant (p = 0.009). Among subjects with the T276T genotype, an increase in triglyceride level was associated with a decrease in adiponectin concentration. This result was not observed in other genotype groups. SNP+45 was not significantly related to serum adiponectin concentration, but high-density lipoprotein (HDL) cholesterol tended to be higher in subjects with the T45T genotype (p = 0.051) compared to subjects with the X45G genotype. In conclusion, the T276T genotype of the adiponectin gene was associated with elevated serum adiponectin level and diastolic blood pressure among young Finnish men.     

Clozapine-induced weight gain associated with the 5HT2C receptor -759C/T polymorphism.

Weight gain has been documented as a significant adverse effect associated with many of the atypical antipsychotic medications. Several recent reports have linked a -759C/T polymorphism of the 5HT2C receptor gene and obesity as well as chlorpromazine, risperidone, and clozapine induced to weight gain. This aim was to determine the association between changes in body mass index (BMI) during clozapine treatment and the -759C/T polymorphism of the 5HT2C receptor gene. This study included 41 patients with treatment-refractory schizophrenia (DSM-IV) who were followed prospectively during treatment with clozapine. Weight and height measurements were obtained prior to starting clozapine and after 6-months of treatment. Genomic DNA was isolated from a whole blood sample and analyzed for the -759C/T polymorphism of the 5HT2C receptor gene. A chi(2) analysis comparing whether or not the subjects carried a -759T allele in subjects grouped as having an increase of more or less than 7% of their baseline BMI during treatment with clozapine found that the presence of the -759T allele was significantly higher in subjects with less than or equal to a 7% increase in baseline BMI compared to those with a greater than 7% increase in BMI. A multiple linear regression analysis showed that both baseline BMI and the presence or absence of the -759T allele had significant effects on 6-month BMI. The T allele may have a protective function in preventing significant weight gain from clozapine. Subjects without the -759T variant allele were at a greater risk for weight gain from clozapine over 6-months compared to those with the -759T allele.     

中老年人群脂联素基因多态性与脑白质病变的关系

目的 探讨在中老年人群中脂联素基因多态性与脑白质病变(WML)之间的关系。方法 纳入2012年6月—2013年1月第三军医大学大坪医院神经内科811例中老年(≥50岁)住院患者的临床资料、血液学指标等进行横断面研究。根据头颅MRI检查结果及Fazekas评分标准诊断WML并分组:诊断为WML者419例纳入观察组,非WML者392例纳入对照组。采用连接酶链反应对患者基因进行分型。应用多因素logistic回归分析脂联素基因多态性与WML关系。结果 与对照组比,观察组平均年龄更大,冠心病、既往卒中史、高血压和糖尿病的比例更高,血浆TC、高密度脂蛋白胆固醇(HDL-C)和载脂蛋白A-Ⅰ浓度较低,空腹血糖浓度较高(P值均<0.05)。rs7649121的AA、AT、TT基因型、等位基因A、T频率在两组间的分布差异有统计学意义(P<0.01)。调整了年龄、性别、既往卒中史、冠心病、高血压、糖尿病和HDL-C后,相对AA基因型,AT基因型和TT基因型仍是WML的独立危险因素;在显性模型中,AT/TT基因型患WML的风险是AA基因型的1.73倍。结论在中国中老年人群中首次发现,脂联素基因的rs7649121位点与WML有关,T等位基因是WML发生的易感基因。     

The Impact of CDH13 Polymorphism and Statin Administration on TG/HDL Ratio in Cardiovascular Patients

Purpose

Adiponectin is expressed in adipose tissue, and is affected by smoking, obesity, and genetic factors, such as CDH13 polymorphism, contributing to the development of coronary vascular diseases (CVDs).

Materials and Methods

We investigated the effect of genetic variations of CDH13 (rs3865188) on blood chemistry and adiponectin levels in 345 CVD patients undergoing statin-free or statin treatment.

Results

Genetic variation in CDH13 was significantly correlated with several clinical factors, including adiponectin, diastolic blood pressure, triglyceride (TG), and insulin levels. Subjects with the T allele (mutant form) had significantly lower adiponectin levels than those with the A allele. Total cholesterol (TC), low-density lipoprotein cholesterol (LDLc), TG/high-density lipoprotein cholesterol (HDLc) ratio, and HDL3b subtype were markedly decreased in statin treated subjects regardless of having the A or T allele. TG and TG/HDL in the statin-free group with TT genotype of the rs3865188 was higher than in the others but they were not different in the statin-treated subjects. We observed a significant difference in adiponectin levels between patients with the A and T alleles in the statin-free group; meanwhile, no difference in adiponectin levels was noted in the statin group. Plasma levels of other cytokines, leptin, visfatin, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), were not different among the CDH13 genotypes according to statin administration. Body mass index (BMI), TG, insulin, HDL3b, and TG/HDL ratio showed negative correlations with adiponectin levels.

Conclusion

Plasma adiponectin levels and TG/HDL ratio were significantly different according to variants of CDH13 and statin administration in Korean patients with CVD.     

Association of the estrogen receptor alpha gene polymorphisms with osteoporosis in the Mexican population

The estrogen receptor gene (ER alpha) has been implicated in the development of osteoporosis. In this study, the association of two ER alpha gene polymorphic markers (a TA dinucleotide repeat and a single nucleotide polymorphism, G2014A) with osteoporosis was tested in 70 osteoporotic women, 70 non-osteoporotic women and 500 subjects from the Mexican population. According to the genetic analysis of the Mexican population using eight unlinked polymorphic markers, we found that our population is structured into three subpopulations; therefore, the allele-phenotype relationship was analyzed with a statistical method that considered population stratification. We found that the G2014A polymorphism is associated with the presence of osteoporosis while the TA dinucleotide repeat is not. The G allele and the GG genotype frequencies of the G2014A marker were significantly higher in osteoporotic than in non-osteoporotic women. Likewise, subjects bearing the G allele in heterozygous or homozygous displayed lower values for lumbar bone mineral density and T score than those who did not present any G allele. The effect of confounders for osteoporosis on the association of G allele-osteoporosis was ruled out. In summary, we conclude that the G2014 polymorphism may become a useful marker for genetic studies of osteoporosis in the Mexican population.     

广东汉族人群脂联素基因多态性与2型糖尿病相关性研究

目的探讨脂联素基因外显子2基因多态性与广东地区汉族人群2型糖尿病的关系。方法以聚合酶链式反应-限制性内切酶长度多态性（PCR-RFLP）技术观察200名健康人与200例2型糖尿病基因外显子2基因多态性。结果2型糖尿病组G/G基因型频率明显高于正常对照组（P〈0.01）,G等位基因频率明显高于正常对照组（P〈0.01）,T等位基因频率明显低于正常对照组（P〈0.01）。结论脂联素基因可能是广东地区汉族人群中2型糖尿病的易感候选基因。     

C-514T polymorphism in hepatic lipase gene promoter is associated with elevated triglyceride levels and decreasing insulin sensitivity in nondiabetic Japanese subjects

Hepatic lipase (HL) is synthesized in the liver and hydrolyses triglyceride and phospholipids. C-514T polymorphism in HL gene promoter was reported to associate with hepatic lipase activity and plasma lipid levels. We examined whether C-514T polymorphism affects glucose metabolism beyond its effect on plasma lipid levels in nondiabetic Japanese subjects. Gene frequencies of C/C homozygote, C/T heterozygote and T/T homozygote were 18, 51 and 31%, respectively. The allelic frequencies of C and T were 44 and 56%, respectively. T allele frequency was much higher than in Caucasian subjects. Moreover, -514T allele carriers had higher levels of triglyceride (P=0.027), fasting insulin (P=0.016) and HOMA-IR (P=0.033) than non-carriers. In contrast to some former studies, -514T allele affected triglyceride levels and insulin sensitivity. Taken together, HL gene might be one of the important susceptibility genes of type 2 diabetes and the high incidence of type 2 diabetes could be explained by high frequency of -514T allele in the Japanese population. Moreover, since HL and adiponectin showed an additive effect on insulin sensitivity, these genetic variations can be independently associated with insulin sensitivity.     

A common functional variant in the interleukin-6 gene is associated with increased body mass index in subjects with type 2 diabetes mellitus

Circulating levels of interleukin-6 (IL-6) are raised in insulin resistant states such as obesity, impaired glucose tolerance (IGT), and type 2 diabetes mellitus (T2DM). Growing evidence suggests that IL-6 is not only produced by fat cells but is also capable of inducing insulin resistance in these cells. The expected result of this in vivo, would be to increase adipose mass and subsequently body mass index (BMI). The IL-6 -174G > C common functional gene variant has consistently been associated with increased plasma IL-6, insulin resistance, and increased cardiovascular risk. We looked at the association between genotype and BMI in 571 Caucasian subjects with T2DM. There was a significant linear association between genotype and BMI: Median (interquartile range) GG 28.8 kg/m2 (26.0-31.6) vs GC; 29.4 kg/m2 (26.3-32.5) vs CC; 30.4 kg/m2 (26.1-33.0), p=0.05. When the group was divided by the median BMI (29.1 kg/m2), 62% of -174CC subjects were in the higher group compared to 38% in the lower group (p=0.008). By contrast, in 2,652 non-diabetic Caucasian men with a median BMI of 26.1 kg/m2, there was no difference in genotype distribution (p=0.288). The frequency of the -174C allele was lower in type 2 diabetes compared to the non-diabetic men (-174C allele frequency: 0.35[0.33-0.38] vs 0.43[0.42-0.45], p <0.00001; -174CC homozygotes: 12.3 vs 18.3%, respectively). The -174C allele is associated with higher BMI in type 2 diabetes, but not amongst healthy subjects. The increased cardiovascular risk associated with the -174C allele may account for the lower frequency of this allele in those with type 2 diabetes.     

肝脂酶基因启动子-250G/A多态性与2型糖尿病合并冠心病易感性的相关研究

目的 探讨汉族人群肝脂酶(hepatic lipase,HL)基因启动子-250G/A多态性与2型糖尿病(type 2 diabetes mellitus,T2DM)合并冠心病(coronary heart disease,CHD)的相关性.方法 采用聚合酶链反应-限制性片段长度多态性方法(polymerase chain reaction-restricted fragment length polymorphism,PCR-RFLP)检测364例T2DM+CHD组、357例T2DM组患者和356名健康对照者HL基因启动子-250G/A多态性,并分析其对脂类的影响.结果 T2DM组与对照组HL基因启动子-250G/A多态性基因型和等位基因频率差异无统计学意义(P>0.05);T2DM+CHD组GA+AA基因型频率低于对照组(0.431 vs 0.618,P=0.031);等位基因频率差异无统计学意义(P>0.05).调整混杂因素后,Spearman相关及线性回归分析,糖尿病患者(T2DM组和T2DM+CHD组),A等位基因与高密度脂蛋白胆固醇、载脂蛋白A1呈正相关;Logistic回归分析显示,A等位基因是冠心病发生的一个危险因素.结论 HL基因启动子-250G/A多态性与2型糖尿病合并冠心病的发生有关,并影响脂类代谢.     

Interleukin-6 gene polymorphism and faster progression to end-stage renal failure in chronic glomerulonephritis

Interleukin-6 (IL-6) is a multifunctional cytokine produced by different cell types, including monocytes, lymphocytes, endothelial and mesangial cells. Deregulated production of IL-6 was found to be involved in mesangial proliferative glomerulonephritis. We investigated whether the single nucleotide polymorphism (SNP) in the promoter region of the IL-6 gene is associated with a development of chronic glomerulonephritis (CGN). The study group consisted of 541 patients with CGN. Of those 338 already progressed to ESRD. The control group involved 253 healthy individuals. All subjects were genotyped for the -634 C/G polymorphism of the IL-6 gene by polymerase chain reaction (PCR). PCR product was digested with BsrBI restriction endonuclease and analyzed on 3% agarose. The allele and genotype frequencies were similar between CGN patients in a pre-dialysis stage and control subjects. Significantly increased frequency of the G allele was observed in the ESRD patients (13% vs. 6% in pre-dialysis stage, P < 0.01). After dividing ESRD patients according to time from reported disease onset to ESRD, those with time < or =5 years showed even higher G allele frequency (21% vs. 13% in entire ESRD group). Interestingly, most of the GG homozygotes were in this faster progressing group. Both subgroups were comparable for sex, age, BMI, total cholesterol and serum creatinine. The multivariate logistic regression analysis revealed that the IL-6 genotype with the G allele was an independent risk factor of progression to ESRD (P < 0.001). Our results indicate that the IL-6 -634 G/C polymorphism may be a possible risk factor for faster progression of chronic glomerulonephritis to ESRD. It is also possible that this polymorphism is in linkage disequilibrium with another functional polymorphism in the II-6 gene or its vicinity.     

Adiponectin gene variation associates with the increasing risk of type 2 diabetes in non-diabetic Japanese subjects

Adiponectin is an adipocyte-secreted protein that is known to modulate insulin sensitivity and glucose homeostasis. A number of genetic variations have been studied. Among them, two single-nucleotide polymorphisms (SNP45T>G, SNP276G>T) showed an association with type 2 diabetes in the Japanese population. In this study, we examined the association between these SNPs and risk factors of type 2 diabetes in 194 non-diabetic Japanese subjects. SNP45 was associated with insulin sensitivity (determined by HOMA-IR, p=0.046) and obesity (body mass index; BMI, p=0.043). SNP276 showed a stronger association with HOMA-IR (p=0.018) and BMI (p=0.017). However, neither SNP had an association with insulin secretion (insulinogenic index) and plasma lipid levels. Moreover, a linkage dis-equilibrium was observed between SNP45 and SNP276. Carriers with SNP45G-SNP276G haplotype had higher BMI (p=0.034) and carriers with SNP45T-SNP276T haplotype had lower BMI (p=0.005) and HOMA-IR (p=0.037). Adiponectin gene variations showed an association with obesity and insulin sensitivity, and adiponectin genotypes may predict the increasing risk for type 2 diabetes in non-diabetic subjects.