{{Rsnum
|rsid=3736228
|Gene=LRP5
|Chromosome=11
|position=68433827
|Orientation=plus
|ReferenceAllele=C
|MissenseAllele=T
|GMAF=0.1354
|Assembly=GRCh38
|GenomeBuild=38.1
|dbSNPBuild=141
|geno1=(C;C)
|geno2=(C;T)
|geno3=(T;T)
|Gene_s=LRP5
}}{{ population diversity
| geno1=(C;C)
| geno2=(C;T)
| geno3=(T;T)
| CEU | 73.9 | 24.3 | 1.8
| HCB | 67.2 | 30.7 | 2.2
| JPT | 50.4 | 44.2 | 5.3
| YRI | 97.3 | 2.7 | 0.0
| ASW | 91.2 | 7.0 | 1.8
| CHB | 67.2 | 30.7 | 2.2
| CHD | 60.6 | 35.8 | 3.7
| GIH | 79.2 | 20.8 | 0.0
| LWK | 96.3 | 3.7 | 0.0
| MEX | 63.2 | 35.1 | 1.8
| MKK | 88.5 | 10.9 | 0.6
| TSI | 79.4 | 19.6 | 1.0
| HapMapRevision=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<sup>-9</sup>), and femoral neck BMD (p = 5.0 x 10<sup>-6</sup>).{{PMID|18349089|OA=1
}}

Note that [[rs4988321]], another [[LRP5]] SNP (also known as Val667Met), was independently associated with BMD in this same study.{{PMID|18349089|OA=1
}}

[http://www.medpagetoday.com/Endocrinology/Osteoporosis/tb/9271 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|OA=1
}} [[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 Summary
|SNP=rs3736228
|PubMedID=18455228
|Condition=Bone mineral density
|Gene=LRP5
|Risk Allele=T
|pValue=6.00E-012
|OR=0.13
|95CI=NR) SD decreas
|OA=1
}}

{{PharmGKB
|RSID=rs3736228
|Name_s=LRP5: A1330V
|Gene_s=LRP5
|Feature=
|Evidence=PubMed ID:19148563
|Annotation=This variant was associated with hip bone mineral density (BMD) in osteoporotic men, but did not appear to be associated with response to risedronate treatment.
|Drugs=risedronate
|Drug Classes=
|Diseases=Osteoporosis
|Curation Level=Curated
|PharmGKB Accession ID=PA164926328
}}

{{PMID Auto
|PMID=20146170
|Title=Association of LPR5 Polymorphism with Bone Mass Density and Cholesterol Level in Population of Chinese Han
}}

{{PMID Auto
|PMID=20960157
|Title=A polymorphism near osteoprotegerin gene confer risk of obesity in Uyghurs
}}

{{PharmGKB
|RSID=rs3736228
|Name_s=
|Gene_s=LRP5
|Feature=
|Evidence=PubMed ID:18455228
|Annotation=This variant is associated with decreased bone mineral density and an increased risk of both osteoporotic fractures and osteoporosis.
|Drugs=
|Drug Classes=
|Diseases=Bone Diseases, Metabolic; Bone Resorption; Fractures, Bone; Hip Fractures; Osteoporosis
|Curation Level=Curated
|PharmGKB Accession ID=PA162316736
}}

{{PharmGKB
|RSID=rs3736228
|Name_s=
|Gene_s=LRP5
|Feature=
|Evidence=PubMed ID:18455228; Web Resource:http://www.genome.gov/gwastudies/
|Annotation=GWAS Results: Bone mineral density, osteoporosis, and osteoporotic fractures: a genome-wide association study (Initial Sample Size: 2,094 women; Replication Sample Size: 6,463 individuals; Risk Allele: rs3736228-T). This variant is associated with Bone mineral density.
|Drugs=
|Drug Classes=
|Diseases=Bone Diseases; Bone Diseases, Metabolic; Fractures, Bone
|Curation Level=Non-Curated
|PharmGKB Accession ID=PA162356407
}}

{{PMID Auto
|PMID=21876774
|Title=Association analysis of canonical Wnt signalling genes in diabetic nephropathy
|OA=1
}}

{{PMID Auto
|PMID=16723389
|Title=Polymorphisms of the low-density lipoprotein receptor-related protein 5 (LRP5) gene are associated with obesity phenotypes in a large family-based association study.
|OA=1
}}

{{PMID Auto
|PMID=17137849
|Title=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.
|OA=1
}}

{{PMID Auto
|PMID=17903296
|Title=Genome-wide association with bone mass and geometry in the Framingham Heart Study.
|OA=1
}}

{{PMID Auto
|PMID=18058054
|Title=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.
|OA=1
}}

{{PMID Auto
|PMID=18588671
|Title=Association between LRP5 polymorphism and bone mineral density: a Bayesian meta-analysis.
|OA=1
}}

{{PMID Auto
|PMID=19181680
|Title=Common variants in the region around Osterix are associated with bone mineral density and growth in childhood.
|OA=1
}}

{{PMID Auto
|PMID=19629617
|Title=Replication study of candidate genes/loci associated with osteoporosis based on genome-wide screening.
|OA=1
}}

{{PMID Auto
|PMID=20072603
|Title=Genome-wide association study identifies ALDH7A1 as a novel susceptibility gene for osteoporosis.
|OA=1
}}

{{PMID Auto
|PMID=20534768
|Title=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.
|OA=1
}}

{{PMID Auto
|PMID=20554715
|Title=Analysis of recently identified osteoporosis susceptibility genes in Han Chinese women.
}}

{{PMID Auto
|PMID=21432225
|Title=A1330V polymorphism of the low-density lipoprotein receptor-related protein 5 gene and bone mineral density in Japanese male workers.
|OA=1
}}

{{PMID Auto GWAS
|PMID=22504420
|Trait=None
|Title=Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture.
|RiskAllele=T
|Pval=2E-26
|OR=0.0800
|ORtxt=None
|OA=1
}}

{{PMID Auto
|PMID=23054017
|Title=The joint effect of cigarette smoking and polymorphisms on LRP5, LEPR, near MC4R and SH2B1 genes on metabolic syndrome susceptibility in Taiwan
}}

{{GET Evidence
|gene=LRP5
|aa_change=Ala1330Val
|aa_change_short=A1330V
|impact=pathogenic
|qualified_impact=Low clinical importance, Uncertain pathogenic
|inheritance=other
|quality_scores=Array
|dbsnp_id=rs3736228
|overall_frequency_n=1186
|overall_frequency_d=10746
|overall_frequency=0.110367
|n_genomes=17
|n_genomes_annotated=0
|n_haplomes=17
|n_articles=3
|n_articles_annotated=3
|qualityscore_in_silico=1
|qualitycomment_in_silico=Y
|qualityscore_case_control=3
|qualitycomment_case_control=Y
|qualityscore_familial=0
|qualitycomment_familial=Y
|qualityscore_severity=2
|qualitycomment_severity=Y
|qualityscore_treatability=4
|qualitycomment_treatability=Y
|gene_in_genetests=Y
|in_gwas=Y
|in_pharmgkb=Y
|genetests_testable=Y
|genetests_reviewed=Y
|nblosum100=2
|autoscore=4
|webscore=N
|n_web_uneval=10
|variant_evidence=0
|clinical_importance=0
|summary_short=In a study of a UK population this variant was associated with a small increased risk of osteoporosis and osteoporotic bone fractures, with each copy of the variant presumed to have an additive effect. A study in Chinese young men failed to find an association with peak bone density.    
}}

{{PMID Auto
|PMID=24130145
|Title=Polymorphism of LRP5, but not of TNFRSF11B, is associated with a decrease in bone mineral density in postmenopausal maya-mestizo women
}}

{{PMID Auto
|PMID=24482712
|Title=Association of LRP5 gene polymorphism with type 2 diabetes mellitus and osteoporosis in postmenopausal women
|OA=1
}}

{{PMID Auto
|PMID=23242660
|Title=Association of LRP5 haplotypes with osteoporosis in Mexican women.
}}

{{PMID Auto
|PMID=25232223
|Title=LRP5 polymorphism-A potential predictor of the clinical outcome in advanced gastric cancer patients treated with EOF regimen
}}
{{on chip | 23andMe v1}}
{{on chip | 23andMe v2}}
{{on chip | 23andMe v3}}
{{on chip | 23andMe v4}}
{{on chip | Affy GenomeWide 6}}
{{on chip | HumanOmni1Quad}}
{{on chip | Illumina Human 1M}}