Our findings demonstrate that polymorphisms in the SHBG promoter predict serum levels of SHBG, androgens, and glucuronidated androgen metabolites, and hip BMD in men.

OBJECTIVE:Human body fat mass is to a large extent genetically determined, but little is known about the susceptibility genes for common obesity. Interleukin-6 (IL-6) suppresses body fat mass in rodents, and IL-6 treatment increases energy expenditure in both rodents and humans. The À174 G/C single-nucleotide polymorphism (SNP) in the IL-6 gene promoter is common in many populations, and À174 C-containing promoters have been found to be weaker enhancers of transcription. Moreover, a SNP at position À572 in the IL-6 promoter has recently been reported to affect transcription. The objective was to investigate the association between the IL-6 gene promoter SNPs and obesity. DESIGN: Trans-sectional association study of IL-6 gene promoter SNPs and indices of obesity. SUBJECTS: Two study populations, the larger one consisting of hypertensive individuals (mean age 57 y, 73% males, n ¼ 485) and the other consisting of 20 y younger nonobese healthy females (n ¼ 74). MEASUREMENTS: Genotyping for the À174 IL-6 G/C and the À572 G/C SNPs, body mass index (BMI), serum leptin levels, serum IL-6 levels, C-reactive protein, fasting blood glucose and various blood lipids. RESULTS: The common À174 C allele (f C ¼ 0.46), but not any À572 allele, was associated with higher BMI and higher serum leptin levels in both study populations. In the larger population, there were significant odds ratios for the association of CC (2.13) and GC (1.76) genotypes with overweight (BMI425 kg/m 2 ). Moreover, as the C allele was common, it accounted for a significant population-attributable risk of overweight (12%; CI 2-21%), although its average effect was modest in this sample. CONCLUSION: Genetically determined individual differences in production of IL-6 may be relevant for the regulation of body fat mass.

The UGT2B15 D85Y and the UGT2B17 deletion polymorphisms are both predictors of the glucuronidation pattern of androgens/androgen metabolites. Our findings indicate that UGT2B17 is involved in 17-glucuronidation of mainly T but also of DHT and androstanediol and that UGT2B15 is involved in the 17-glucuronidation of androstanediol. Furthermore, these two polymorphisms are predictors of fat mass in men.

ABSTRACT:The association between aromatase gene polymorphisms, bone parameters, and sex steroid levels was studied in 1068 men (18.9 ± 0.6 years of age). Several aromatase gene polymorphisms were found to be associated with serum testosterone levels and cortical bone size but not with trabecular volumetric BMD.Introduction: Both testosterone and estrogens are important for the male skeleton. Aromatase, the product of the CYP19 gene, is the key enzyme in the conversion of testosterone to estradiol. A functional aromatase enzyme has been shown to be crucial for the normal development of the male skeleton. The role of genetic polymorphisms in the aromatase gene for trabecular volumetric BMD (vBMD) and cortical bone size has not previously been studied in men. Materials and Methods:The Gothenburg Osteoporosis and Obesity Determinants (GOOD) study consists of 1068 men (18.9 ± 0.6 years of age). The TTTA repeat polymorphism (TTTA n ) and three single nucleotide polymorphisms (SNPs), including the Val 80 SNP, in the CYP19 gene, were analyzed. Serum levels of testosterone and estradiol were measured. Areal BMD (aBMD) was measured by DXA, whereas cortical and trabecular vBMD and cortical bone size were measured by pQCT. Results: The TTTA n and the Val 80 genotypes were independent predictors of aBMD of the radius, lumbar spine, total body, and cortical bone size (cortical cross-sectional area and thickness) of both the radius and tibia. In contrast, trabecular vBMD was not associated with CYP19 polymorphisms. Homozygosity for the long allele (>9 repeats) of the TTTA n and for the G allele of the Val 80 SNP was associated with the highest aBMD and testosterone levels as well as with the greatest cortical bone size. Regression analyses indicated that the association with aBMD was mediated through affected cortical bone size. Conclusions:We showed, in a large well-characterized cohort of men at the age of peak bone mass, that several common aromatase polymorphisms are associated with cortical bone size but not with trabecular vBMD. One may speculate that affected CYP19 activity, resulting in altered testosterone levels during pubertal development, might contribute to the association between CYP19 polymorphisms and cortical bone size.

The present study indicates that the NPY T1128C polymorphism is an independent predictor for myocardial infarction and stroke in a Swedish hypertensive population.