title: Relationship among VDR (BsmI and FokI), COLIA1, and CTR polymorphisms with bone mass, bone turnover markers, and sex hormones in men.
abstract: Osteoporosis is a disease characterized by low bone mineral density (BMD) and up to 80% of its variance is under genetic control. Although osteoporosis is more frequent in women, one-third of hip fractures also occur in men. Much information on genetic factors and bone density has been obtained in women, but only a few studies have been performed in osteoporotic men. We have evaluated the relationship between polymorphisms for several candidate genes such as vitamin D receptor (VDR), collagen type Ia1 (COLIA1), and calcitonin receptor (CTR) in a sample of unrelated Italian men (n = 253, mean age 58.41 +/- 15.64 SD). We found no significant differences in BMD when subjects were stratified for their VDR (BsmI and FokI) and COLIA1 genotypes. BMD both at the lumbar spine and at the femoral neck were associated with polymorphism of CTR gene. The CC genotype of CTR gene had the lowest BMD value (P <0.05 and P <0.01 at the spine and hip, respectively) and its prevalence was significantly over-represented in the subgroup of men with prior hip or vertebral fracture as compared with controls (P = 0.004% c2 = 11.10). The men with the CC genotype also showed significantly lower body mass index (BMI), serum sex hormone binding globulin (SHBG), estradiol, total alkaline phosphatase-(total AP) and bone alkaline phosphatase (bone AP) levels and significantly higher free androgen index (FAI). In conclusion, the polymorphism of CTR gene but not VDR and COLIA1 is associated with osteoporosis incidence and the levels of alkaline phosphatase and estradiol. The lower BMD in CC genotype is apparently associated in males with depressed bone formation and lower estradiol levels.
authors.affiliation: Rheumatology Unit, Valeggio S/M, University of Verona, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Braga
authors.forename: A
authors.initials: A
authors.lastname: Sangalli
authors.forename: G
authors.initials: G
authors.lastname: Malerba
authors.forename: M
authors.initials: M
authors.lastname: Mottes
authors.forename: S
authors.initials: S
authors.lastname: Mirandola
authors.forename: D
authors.initials: D
authors.lastname: Gatti
authors.forename: M
authors.initials: M
authors.lastname: Rossini
authors.forename: M
authors.initials: M
authors.lastname: Zamboni
authors.forename: S
authors.initials: S
authors.lastname: Adami
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000469:Alkaline Phosphatase / Q000097:blood; D015415:Biomarkers / Q000097:blood; D015519:Bone Density / Q000235:genetics; D016723:Bone Remodeling / Q000235:genetics; D024042:Collagen Type I / Q000235:genetics* / Q000378:metabolism; D004958:Estradiol / Q000097:blood; D005272:Femur Neck / Q000000981:diagnostic imaging / Q000378:metabolism; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D011110:Polymorphism, Genetic; D011859:Radiography; D018003:Receptors, Calcitonin / Q000235:genetics*; D018167:Receptors, Calcitriol / Q000235:genetics*; D012738:Sex Hormone-Binding Globulin / Q000032:analysis; D016329:Sp1 Transcription Factor / Q000235:genetics; D013739:Testosterone / Q000097:blood
chemical_list: D015415:Biomarkers; D024042:Collagen Type I; D018003:Receptors, Calcitonin; D018167:Receptors, Calcitriol; D012738:Sex Hormone-Binding Globulin; D016329:Sp1 Transcription Factor; D013739:Testosterone; D004958:Estradiol; D000469:Alkaline Phosphatase