LAMC1 gene is associated with premature ovarian failure.
OBJECTIVE
Common variations with modest effect in complex and polygenic disease such as premature ovarian failure (POF) can be detected by a genome wide association study. We performed a genome wide association study to identify predisposing genes associated with an increased risk of POF.


METHODS
In stage I, genome wide association study was performed using 24 POF patients and 24 matched controls. A strongly associated region was re-tested to confirm the association with POF in stage II using 98 patients and 218 matched controls.


RESULTS
In the stage I, we found a strongly associated region that was located on chromosome 1q31 and encoded the laminin gamma 1 (LAMC1) gene. All 22 single nucleotide polymorphisms (SNPs) in the LAMC1 formed a linkage disequilibrium block and two haplotypes were significantly associated with POF. In the stage II, 14 SNPs, the majority of which were SNPs located in coding region and tagging SNPs, were genotyped. Distributions of 9 SNPs of them including one nonsynonymous SNP (rs20558) and one haplotype (HT1, C-C-T-G-C-C-A-T-T-C) were significantly higher in POF patients than in control group (86.6% and 74.5%, respectively, OR=2.209, CI: 1.139-4.284, P=0.017).


CONCLUSIONS
We showed for the first time that LAMC1 is significantly associated with POF, and specifically, possession of at least one HT1 was associated with susceptibility to POF. This result means that HT1 may co-exist with causative variant for susceptibility to POF in linkage disequilibrium and that the LAMC1 may be involved in POF pathogenesis.
Department of Biomedical Science, College of Life Science, CHA University, 463-836 Seongnam-si, Gyeonggi-do, Republic of Korea.
Jung-A
JA
Pyun
Dong Hyun
DH
Cha
KyuBum
K
Kwack
D016022:Case-Control Studies; D002878:Chromosomes, Human, Pair 1; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007797:Laminin / Q000235:genetics*; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide; D016649:Primary Ovarian Insufficiency / Q000235:genetics*; D012307:Risk Factors
D007797:Laminin; C089141:laminin gamma 1