rs3736228

plus

Geno	Mag	Summary
(C;C)	0	normal
(C;T)	1.3	increased risk for osteoporosis
(T;T)	1.7	increased risk for osteoporosis

Reference

GRCh38 38.1/141

Chromosome

11

Position

68433827

Gene

LRP5

is a	snp
is	mentioned by
dbSNP	rs3736228
dbSNP (classic)	rs3736228
ClinGen	rs3736228
ebi	rs3736228
HLI	rs3736228
Exac	rs3736228
Gnomad	rs3736228
Varsome	rs3736228
LitVar	rs3736228
Map	rs3736228
PheGenI	rs3736228
Biobank	rs3736228
1000 genomes	rs3736228
hgdp	rs3736228
ensembl	rs3736228
geneview	rs3736228
scholar	rs3736228
google	rs3736228
pharmgkb	rs3736228
gwascentral	rs3736228
openSNP	rs3736228
23andMe	rs3736228
SNPshot	rs3736228
SNPdbe	rs3736228
MSV3d	rs3736228
GWAS Ctlg	rs3736228

GMAF

0.1354

Max Magnitude

1.7

?

(C;C) (C;T) (T;T)

28

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).[PMID 18349089 ]

Note that rs4988321, another LRP5 SNP (also known as Val667Met), was independently associated with BMD in this same study.[PMID 18349089 ]

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.

[PMID 18455228 ] 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.[PMID 19148563]

GWAS
SNP	rs3736228
PubMedID	[PMID 18455228 ]
Condition	Bone mineral density
Gene	LRP5
Risk Allele	T
pValue	6.00E-012
OR	0.13
95% CI	NR) SD decreas

[PMID 20146170] Association of LPR5 Polymorphism with Bone Mass Density and Cholesterol Level in Population of Chinese Han

[PMID 20960157] A polymorphism near osteoprotegerin gene confer risk of obesity in Uyghurs

[PMID 21876774 ] Association analysis of canonical Wnt signalling genes in diabetic nephropathy

[PMID 16723389 ] Polymorphisms of the low-density lipoprotein receptor-related protein 5 (LRP5) gene are associated with obesity phenotypes in a large family-based association study.

[PMID 17137849 ] Genetic variation at the low-density lipoprotein receptor-related protein 5 (LRP5) locus modulates Wnt signaling and the relationship of physical activity with bone mineral density in men.

[PMID 17903296 ] Genome-wide association with bone mass and geometry in the Framingham Heart Study.

[PMID 18058054 ] Polymorphisms in the low-density lipoprotein receptor-related protein 5 (LRP5) gene are associated with peak bone mass in non-sedentary men: results from the Odense androgen study.

[PMID 18588671 ] Association between LRP5 polymorphism and bone mineral density: a Bayesian meta-analysis.

[PMID 19181680 ] Common variants in the region around Osterix are associated with bone mineral density and growth in childhood.

[PMID 19629617 ] Replication study of candidate genes/loci associated with osteoporosis based on genome-wide screening.

[PMID 20072603 ] Genome-wide association study identifies ALDH7A1 as a novel susceptibility gene for osteoporosis.

[PMID 20534768 ] OPG and RANK polymorphisms are both associated with cortical bone mineral density: findings from a metaanalysis of the Avon longitudinal study of parents and children and gothenburg osteoporosis and obesity determinants cohorts.

[PMID 20554715] Analysis of recently identified osteoporosis susceptibility genes in Han Chinese women.

[PMID 21432225 ] A1330V polymorphism of the low-density lipoprotein receptor-related protein 5 gene and bone mineral density in Japanese male workers.

GWAS snp
PMID	[PMID 22504420 ]
Trait
Title	Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture.
Risk Allele	T
P-val	2E-26
Odds Ratio	0.0800 None

[PMID 23054017] The joint effect of cigarette smoking and polymorphisms on LRP5, LEPR, near MC4R and SH2B1 genes on metabolic syndrome susceptibility in Taiwan

[PMID 24130145] Polymorphism of LRP5, but not of TNFRSF11B, is associated with a decrease in bone mineral density in postmenopausal maya-mestizo women

[PMID 24482712 ] Association of LRP5 gene polymorphism with type 2 diabetes mellitus and osteoporosis in postmenopausal women

[PMID 23242660] Association of LRP5 haplotypes with osteoporosis in Mexican women.

[PMID 25232223 ] LRP5 polymorphism-A potential predictor of the clinical outcome in advanced gastric cancer patients treated with EOF regimen

[PMID 27582019 ] Low density lipoprotein receptor-related protein 5 gene polymorphisms and osteoporosis in Thai menopausal women.

ClinVar
Risk	Rs3736228(T;T)
Alt	Rs3736228(T;T)
Reference	Rs3736228(C;C)
Significance	Non-pathogenic
Disease	not specified
Variation	info
Gene	LRP5
CLNDBN	not specified
Reversed	0
HGVS	NC_000011.9:g.68201295C>T
CLNSRC
CLNACC	RCV000242123.2,