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.

Genetic Polymorphisms in Calcitonin Receptor Gene and Risk for Recurrent Kidney Calcium Stone Disease

“…There is a large body of evidence relating the L447P of the CALCR to osteoporosis or bone fracture [9,10,11,12,13]. Recently the 3 ′ UTR+18C>T polymorphism has also been observed to be strongly associated with osteoporosis and bone fracture in a Korean population [21].…”

“…Some calcitonin receptor gene (CALCR) polymorphisms have been shown to be associated with bone mineral density in different populations [9,10,11,12,13]. Researchers have investigated the association of CALCR polymorphisms with urolithiasis, all identifying only a single nucleotide polymorphism (SNP) ( L447P polymorphism) [4,5,14], in which thymine (T) has been replaced by cytosine (C), causing a change from leucine to proline in the 447th amino acid.…”

Vitamin D metabolism, sex hormones, and male reproductive function

“…Numerous studies investigated the putative physiological relationship between circulating levels of 25OHD 3 /1,25(OH) 2 D, the activity of VDR and VD metabolizing enzymes, and serum testosterone and estradiol levels in both animals and humans (Tanaka et al 1976, Hyldstrup et al 1984, Small et al 1984, Hochberg et al 1985, Krabbe et al 1986, Sonnenberg et al 1986, Hagenfeldt et al 1992, Morley et al 1993, Inpanbutr et al 1996, Otremski et al 1997, Rapado et al 1999, Kinuta et al 2000, van Abel et al 2002, Braga et al 2002, Van Cromphaut et al 2003, Echchgadda et al 2004, Valimaki et al 2004, Kastelan et al 2009, Fleet & Schoch 2010, Krishnan et al 2010a, 2010b, Meng et al 2010, Pilz et al 2011, Ramlau-Hansen et al 2010, Wehr et al 2010, Ceglia et al 2011, Foresta et al 2011, Lundqvist et al 2011, Lee et al 2012. It has been shown that estrogen promotes the two-step activation of cholecalciferol to 1,25(OH) 2 D 3 and reinforces a positive effect on calcium homeostasis through a direct stimulatory effect on intestinal calcium absorption.…”

Genetic predisposition for femoral neck stress fractures in military conscripts

“…Studies in postmenopausal women revealed that the CC genotype is more common in non-osteoporotic women than the TT genotype [30,31], and that the TT genotype is associated with lower lumbar spine and femoral neck BMD and increases the predisposition for osteoporosis [32,33]. The opposite finding was suggested by Braga et al [34] who reported that the CC genotype is associated with decreased BMD and is more common in men with hip or vertebral fractures than in control subjects [34]. In our study, the CTR allele C together with a VDR C-A haplotype appeared to protect subjects from fractures.…”