The UGT2B17 gene polymorphism and bone mineral density in puberty.

• Main Author: Sohail, Isma
• Other Authors: Jens Petter Berg
• Format: Master Thesis
• Language: English
• Published: 2008
• Subjects: medisinsk biokjemi; VDP::726; Tromsø
• Online Access: http://hdl.handle.net/10852/29481; http://urn.nb.no/URN:NBN:no-20783

BACKGROUND: The uridine diphosphate-glucuronosyltransferase B17 is important for the excretion and thereby inactivation of testosterone. Testosterone is important for the bone growth in puberty. Low values of this hormone can cause male hypogonadism. Here we determine if there is any relationship between the UGT2B17 polymorphism and bone growth in puberty. Our agenda was to find if the distribution of the genotypes (insertion/insertion, insertion/deletion and deletion/deletion) were different for the groups with the highest increase in bone mass. Also we wanted to find out if there was any relationship between the UGT2B17 polymorphism and male hypogonadism. At last we studied if the polymorphism is associated with postmenopausal bone mass and loss. METHODS: The DNA samples used in this study were selected from three different groups 1) a cohort of children and adolescents recruited for studies of bone growth by Prof. Jens P Berg, Hormone Laboratory, Aker university hospital and UiO, 2) a substudy of male hypogonadism in the fourth survey of the Tromsø study by Prof. Johan Svartberg, UNN and UiTø, and 3) a study of postmenopausal bone loss (BUS-study) by Prof. Jan A. Falch, Endocrine Clinic, Aker university hospital and UiO. Genotyping was performed using primers for the insertion and deletion gene. The products were amplified using polymerase chain reaction (PCR) and separated on gel. RESULTS: There was a correlation between the gain in bone mineral density ultradistal forearm (BMDud) for boys in the puberty and the UGT2B17 polymorphism (p=0,009). The gain in BMDud was higher in boys homozygous for the UGT2B17 deletion polymorphism (0.100±0.037) compared with homozygotes for the insertion polymorphism (0.060±0.040) and heterozygotes (0.071±0.041). A statistically significant relationship was found between the UGT2B17 polymorphism and BMD of trochanter major (p=0.017) and the BMD of total hip (p=0.016) for the whole group. The BMD of trochanter major showed higher values for the UGT2B17 deletion/deletion genotype (0.845±0.147) compared with the insertion/insertion genotype (0.786±0.115) and heterozygotes (0.767±0.119).Additionally, BMD of the total hip also showed higher values for the UGT2B17 deletion/deletion genotype (1.05±0.155) compared with the insertion/insertion genotype (0.992±0.131) and heterozygotes (0.962±0.138). The association between BMD of trochanter major and the UGT2B17 polymorphism was also found for the boys analysed separately (p=0.02). There was also a statistically significant higher value for the UGT2B17 deletion/deletion genotype (0.904±0.157) compared with the insertion/insertion genotype (0.791±0.129) and heterozygotes (0.788±0.129). Substudy 2: There was no association between male hypogonadism and the UGT2B17 polymorphism. Substudy 3: There was no association between postmenopausal bone mass and loss and the UGT2B17 gene polymorphism. DISCUSSION: The UGT2B17 gene polymorphism is playing a role in determining the bone mineral density in the puberty. The deletion/deletion polymorphism is associated with a higher serum IGF-1 value again stimulates to a higher bone mineral density in the puberty".