Koek et al.: The T-13910C polymorphism in the lactase phlorizin hydrolase gene is associated with differences in serum calcium levels and calcium intake
Koek, W; van Meurs, J; van der Eerden, B; Rivadeneira, F; Zillikens, M; Hofman, A; Obermayer-Pietsch, B; Lips, P; Pols, H; Uitterlinden, A; van Leeuwen, J.
The T-13910C polymorphism in the lactase phlorizin hydrolase gene is associated with differences in serum calcium levels and calcium intake.
J Bone Miner Res. 2010; 12(3): PubMed FullText FullText_MUG
- INTRODUCTION: The C-variant of a T-13910C polymorphism (rs4988235; NT_022135.15:g.25316568G>A) upstream of the lactase phlorizin hydrolase (LPH) gene causes lactose intolerance. Association studies with differences in bone parameters and fracture risk have been inconclusive. OBJECTIVE: To study the association of LPH rs4988235 with body height and bone parameters and calcium homeostasis in two elderly populations of Dutch Caucasians, and assess interaction with vitamin D receptor (VDR polymorphisms. MATERIALS AND METHODS: Genotyping of LPH and VDR polymorphisms was performed in 6367 individuals from the Rotterdam Study and 844 from the Longitudinal Aging Study Amsterdam (LASA). Associations with age, height, weight, bone mineral density (BMD), skeletal morphometric parameters and serum vitamin D and calcium levels, and dietary calcium intake were assessed using ANOVA or analysis of covariance, and allele dose effect using linear regression analysis. Fracture risk was analyzed using Cox's proportional hazard regression analysis. RESULTS: Associations with body height (p= 2.7x10(-8)) and vertebral area (p=0.048) found in the Rotterdam study were explained by population stratification as assessed by principal component analyses and disappeared after additional adjustments. No associations with femoral neck or lumbar spine BMD or with fracture risk were detected. Calcium intake and serum ionized serum calcium were significantly lower in C-homozygotes (p=9.2x10(-7)' p=0.02, respectively). For none of the parameters studied interaction between the T-13910C polymorphism and VDR block 5 haplotype 1 was observed. CONCLUSION: We show that the C-allele of the T-13910C polymorphism causing lactose intolerance is associated with lower dietary calcium intake and serum calcium levels but not with BMD or fractures. The associations observed with height and vertebral area were the result of population stratification. This demonstrates the impact of population stratification and urges to carefully take this into account on genetic associations, in particular in these dietary intake-related phenotypes of which LPH and lactose intolerance are a strong example. (c) 2010 American Society for Bone and Mineral Research.