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Unlabelled: In a candidate gene association study, we found that SMAD2 promoter alleles and haplotypes were significantly associated with bone mineral density (BMD) at the lumbar spine and various proximal femur sites. Our results suggest that SMAD2 polymorphisms may be one of genetic determinants of BMD in postmenopausal women., Introduction: SMAD2, which is the specific intracellular transducer of TGF-ß, is thought to participate in bone metabolism by playing a critical role in the development and function of osteoclasts and osteoblasts. We performed association analyses of the genetic variation in SMAD2 to ascertain the contribution of this gene to BMD and risk of osteoporotic fracture., Methods: We selected three SMAD2 promoter single-nucleotide polymorphisms (SNPs) based on heterozygosity and validation status. Postmenopausal Korean women (n = 1,329) were genotyped for these SNPs, and their BMD and risk of fractures were assessed. BMD at the lumbar spine and proximal femur was measured using dual-energy X-ray absorptiometry. P values were corrected for multiple testing by the effective number of independent marker loci (P (cor))., Results: We found that SMAD2 -35302C>T, -34952A>G, and ht2 were significantly associated with BMD at both the lumbar spine and femur neck (P (cor) = 0.020-0.046), whereas SMAD2 -36201A>G and ht1 affected the femur neck BMD (P (cor) = 0.018-0.031). The genetic effects of these three polymorphisms on BMD at the lumbar spine and femur neck were risk-allele dependent in additive model. The three polymorphisms and two hts were also significantly associated with BMD at other proximal femur sites, such as the total femur, trochanter, and femur shaft (P (cor) = 0.001-0.046). However, none of the polymorphisms or hts was associated with an increased risk of fracture., Conclusions: Our results suggest that SMAD2 polymorphisms may be one of genetic determinants of BMD in postmenopausal women.

To investigate whether microalbuminuria is associated with the insulin resistance syndrome independent of hypertension and type 2 diabetes, we studied the association between microalbuminuria and features of insulin resistance syndrome in Korean general population. We selected 1006 subjects by a random cluster sampling among residents aged >40 years living in the Chung-Up district, a rural area of South Korea. Subjects were stratified by oral glucose tolerance status [normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and diabetes mellitus], and by the presence or absence of hypertension. Urinary albumin excretion rate (UAER) was determined using timed overnight urine collection. Various cardiovascular risk factors including anthropometric indices, serum lipid, true insulin and proinsulin concentrations were also measured. The prevalence of microalbuminuria (UAER between 20 and 200 microg/min) increased as the glucose tolerance worsened (6.0% in NGT, 11.8% in IGT, and 21.8% in diabetes; chi(2) trend=25.9, P<0.001). Subjects with microalbuminuria had a higher body mass index (BMI), waist-to-hip circumference ratio (WHR), systolic and diastolic blood pressure (BP), fasting and 2 h plasma glucose, fasting plasma insulin and proinsulin levels, and lower HDL-cholesterol level than subjects without microalbuminuria. In multiple regression analysis, BMI, diastolic BP, 2 h plasma glucose, and fasting plasma insulin levels were found to be independent factors associated with UAER. Multiple logistic regression analysis showed that not only diabetes mellitus and hypertension, but also fasting hyperinsulinemia and waist-to-hip ratio were independent factors associated with the presence of microalbuminuria. When the normotensive, non-diabetic subjects were analyzed separately, fasting hyperinsulinemia and impaired glucose tolerance remained independent variables associated with the presence of microalbuminuria. These results show that microalbuminuria in the Korean general population is associated with hyperinsulinemia and central obesity, and suggest that microalbuminuria is a feature of the insulin resistance syndrome independent of hypertension or type 2 diabetes.