Adiponectin gene SNP276 variants and central obesity confer risks for hyperglycemia in indigenous Taiwanese.

This cross-sectional study analyzed the effects of two single nucleotide polymorphisms (SNP) of the adiponectin gene, SNP45 and SNP276, on hyperglycemia in indigenous Taiwanese, and whether central obesity modulates the effects of these SNPs. Overall, 550 indigenous Taiwanese were recruited for this cross-sectional study. The subjects were categorized into a hyperglycemic group if fasting plasma glucose was > 126 mg/dL (n = 88) or the control group if fasting plasma glucose was < 100 mg/dL (n = 462). The SNP276 TT homozygote carried greater hyperglycemia risk than SNP276 GG [odds ratio (OR) = 2.67, 95% confidence interval (CI) = 1.05-6.78], but not heterozygote (OR = 1.54, 95% CI = 0.95-2.50). SNP45 T > G was not associated with hyperglycemia risk. In multivariate-adjusted modeling, we found a significant relationship between SNP276 T carriers (GT + TT) (OR = 2.06, 95% CI = 1.10-3.88) and central obesity (OR = 4.50, 95% CI = 1.91-10.61) with hyperglycemia. Compared with non-central-obese carriers of SNP276 GG, non-central-obese SNP276 T carriers, and central obese subjects with SNP276 GG and SNP276 T carriers had 5.50, 8.31 and 13.76-fold, respectively, higher risks for hyperglycemia; obese carriers of the T-containing variants experienced a combined risk for hyperglycemia. Furthermore, the hyperglycemic risks were more pronounced in leaner (non-central-obese) individuals carrying the T variant than the central-obese individuals. The adiponectin SNP276 T variant and central obesity had independent and additive effects on hyperglycemia risks. These findings may provide valuable information regarding preventive strategies that might be useful to prevent or treat diabetes and its related complications.

Combinational polymorphisms of seven CXCL12-related genes are protective against breast cancer in Taiwan.

Many single nucleotide polymorphisms (SNPs) have been found to be associated with breast cancer, but their SNP interactions are seldom addressed. In this study, we focused on the joint effect for SNP combinations of seven CXCL12-related genes involved in major cancer-related pathways. SNP genotyping was determined by PCR-restriction fragment length polymorphism (RFLP) in this study (case = 220, control = 334). Different numbers of combinational SNPs with genotypes called the SNP barcodes from different chromosomes were used to evaluate their joint effect on breast cancer risk. Except for vascular endothelial growth factor (VEGF) rs3025039-CT, none of these SNPs were found to individually contribute to breast cancer risk. However, for two combined SNPs, the proportion of subjects with breast cancer was significantly low in the SNP barcode with CC-GG genotypes in rs2228014-1801157 (CXCR4-CXCL12) compared to those with non-CC-GG genotypes. Similarly, the SNP barcode of rs12812942-rs2228014-rs3025039 (CD4-CXCR4-VEGF) and rs12812942-rs3136685-rs2228014-rs1801157 (CD4- CCR7-CXCR4-CXCL12) with specific genotype patterns (AT-CC-CC and AT-AG-CC-GG) among three and four combinational SNPs were significantly low in breast cancer occurrence. More SNP combinations larger than five SNPs were also addressed, and these showed similar effects. After controlling for age, and comparing their corresponding non-SNP barcodes, the estimated odds ratios for breast cancer ranged between 0.20 and 0.71 for specific SNP barcodes with two to seven SNPs. In conclusion, we have associated the potential combined CXCL12-related SNPs with genotypes that were protective against breast cancer, and that may contribute to identification of a low-risk population for the development of breast cancer.

SNP combinations in chromosome-wide genes are associated with bone mineral density in Taiwanese women.

Osteoporosis is a major public health problem, mainly quantified by low BMD. Eleven polymorphisms were investigated in this study; TNFalpha-857 (rs1799724), TGFbeta1-509 (rs1800469), osteocalcin (rs1800247), TNFalpha-308 (rs1800629), PTH BstB I (rs6254), PTH Dra II (rs6256), IL-1ra (VNTR), HSP70 hom (rs2227956), HSP 70-2 (rs1061581), CTR (rs1801197), and BMP-4 (rs17563). The relationship between the combined polymorphisms in different genomic regions and BMD variation was investigated. Among the female subjects, the proportion of subjects with low BMD in low BMI group (< or = 18.50) was significantly higher than that of the middle (18.51-22.99) and high (> or = 23.00) BMI groups (P < 0.05). In post-menopausal women, there was a significant association between low BMD and genotypes ranging from 2 to approximately 7 SNPs. For two combined SNPs, the portion of subjects with low BMD was significantly higher in those with CC-AA genotypes in rs1799724-rs1800629, compared to those with non-CC-AA genotypes in post-menopausal women and the combination of all women. Similarly, part of the combined SNPs with rs1799724-rs1800629-rs6254-rs6256-IL-1ra-rs2227956-rs1801197 was significantly associated with reduced BMD. After controlling for age and BMI, post-menopausal women with certain specific SNP combination had a 3.54- to 4.68-fold increased risk for low BMD, comparing to other SNP combinations. In conclusion, our data suggest that several gene polymorphisms may be cooperatively involved in the development of osteoporosis.

De novo 617G-A nucleotide mutation in the ACVR1 gene in a Taiwanese patient with fibrodysplasia ossificans progressiva.

Fibrodysplasia ossificans progressiva (FOP) is a rare congenital disease with autosomal dominant transmission characterized by the presence of malformations of the big toes and of postnatal progressive heterotopic endochondral osteogenesis. We report the case of 3-year-old girl with dysplasia of the first metatarsal bones and progressive heterotopic ossificans of the right thigh due to previous diphtheria-tetanus-pertussis immunizations and several inappropriate surgical interventions. Direct sequence analysis identified a 617G-A nucleotide mutation in the patient but not in her parents or brother. Pedigree analysis suggests that a de novo mutation in the ACVR1 gene is responsible for the disease in this family. This is the first report of the results of a mutation analysis in a sporadic case of FOP in a Taiwanese patient.

G-2548A polymorphism of the leptin gene is correlated with extreme obesity in Taiwanese aborigines.

We examined the genetic associations of the G-2548A polymorphism in the promoter of the leptin (LEP) gene and the Gln223Arg (Q223R) polymorphism of the leptin receptor (LEPR) gene with obesity. Two hundred twenty-six obese aboriginal subjects (BMI > or = 27 kg/m2) and 182 aboriginal subjects with normal weight (BMI < 25 kg/m2) participated in this study. The polymorphisms of LEP G-2548A and LEPR Q223R were genotyped by polymerase chain reaction/restriction fragment length polymorphism, and their anthropometric characteristics were measured. Levels of leptin, triglycerides, and cholesterol were measured after overnight fasting. We found that the frequencies of the LEP G/G homozygote (22.6%) with Mendelian recessive (chi2 = 7.89, p = 0.005) and codominant (chi2 = 7.93, p = 0.02) models to be higher in the extremely obese subjects (BMI > or = 35 kg/m2) than in normal weight subjects (6.9%) but not in moderately obese subjects (35 > BMI > or = 27 kg/m2). There was no difference in genotypic frequency of the LEPR Q223R polymorphism between the extreme obese and control groups. We suggest that the LEP -2548 G/G homozygote plays a genetic recessive role in the development of extreme obesity in Taiwanese aborigines.