Rs3736228

rs3736228 is a SNP in the LRP5 gene that is also known as Ala1330Val or A1330V; the more common (C) allele encodes the Ala (alanine), while the rarer (T) allele encodes the Val (valine), which is the risk allele.

rs3736228(T) is associated with vertebral fractures and reduced bone mineral density (BMD), with an overall odds ratio for fractures of 1.06 per allele (CI: 1.01-1.12; 7802 fractures among 31,199 individuals studied). More specifically, the rs3736228(T) allele was associated with reduced lumbar spine BMD (p = 2.6 x 10-9), and femoral neck BMD (p = 5.0 x 10-6).

Note that rs4988321, another LRP5 SNP (also known as Val667Met), was independently associated with BMD in this same study.

news rs3736228 was associated with a 30% increase in the risk of both osteoporosis and osteoporotic fractures. Both increases were significant, at P=0.002 and P=0.008, respectively.

rs3736228 associated with decreased bone mineral density (p=6.3x10(-12) for lumbar spine and p=1.9x10(-4) for femoral neck) and an increased risk of both osteoporotic fractures (odds ratio [OR] 1.3, 95% CI 1.09-1.52, p=0.002) and osteoporosis (OR 1.3, 1.08-1.63, p=0.008).

rs4355801 associated with decreased bone mineral density (p=7.6x10(-10) for lumbar spine and p=3.3x10(-8) for femoral neck) and increased risk of osteoporosis (OR 1.2, 95% CI 1.01-1.42, p=0.038).

The presence of both risk alleles increased the risk of osteoporotic fractures (OR 1.3, 1.08-1.63, p=0.006) and this effect was independent of bone mineral density.

A later study (2009) also found an association between rs3736228 and hip BMD; subjects with rs3736228(T;T) genotypes had 8.4% higher total-hip BMD compared to other genotypes (p = 0.009) at baseline in a study of 249 osteoporotic Caucasian men.