Calpain-10 variants and haplotypes are associated with polycystic ovary syndrome in Caucasians.
PCOS is known to be associated with an increased risk of T2DM and has been proposed to share a common genetic background with T2DM. Recent studies suggest that the Calpain-10 gene (CAPN10) is an interesting candidate gene for PCOS susceptibility. However, contradictory results were reported concerning the contribution of certain CAPN10 variants, especially of UCSNP-44, to genetic predisposition to T2DM, hirsutism, and PCOS. By means of MALDI-TOF MS technique, we genotyped an expanded single nucleotide polymorphism panel, including the CAPN10 UCSNP-44, -43, -56, ins/del-19, -110, -58, -63, and -22 in a sample of 146 German PCOS women and 606 population-based controls. Statistical analysis revealed an association between UCSNP-56 and susceptibility to PCOS with an odds ratio (OR) of 2.91 (95% CI=1.51-5.61) for women carrying an AA genotype compared with GG. As expected, the 22-genotype of the ins/del-19 variant, which is in high linkage disequilibrium (r2=0.98) with UCSNP-56, was also significantly associated (OR=2.98, 95% CI=1.55-5.73). None of the additionally tested variants alone showed any significant association with PCOS. A meta-analysis including our study (altogether 623 PCOS cases and 1,224 controls) also showed significant association only with ins/del-19. The most common haplotype TGG3AGCA was significantly associated with a lower risk for PCOS (OR=0.487, P=0.0057). In contrast, the TGA2AGCA haplotype was associated with an increased risk for PCOS (OR=3.557, P=0.0011). By investigating a broad panel of CAPN10 variants, our results pointed to an allele dose-dependent association of UCSNP-56 and ins/del-19 with PCOS.
Vollmert
Caren
C
Institute of Epidemiology, GSF-National Research Center for Environment and Health, Institute of Epidemiology, Ingolstädter Landstrasse 1, D-85764 Neuherberg, Germany. vollmert@gsf.de
Hahn
Susanne
S
Lamina
Claudia
C
Huth
Cornelia
C
Kolz
Melanie
M
Schöpfer-Wendels
Andreas
A
Mann
Klaus
K
Bongardt
Friedhelm
F
Mueller
Jakob C
JC
Kronenberg
Florian
F
Wichmann
H-Erich
HE
Herder
Christian
C
Holle
Rolf
R
Löwel
Hannelore
H
Illig
Thomas
T
Janssen
Onno E
OE
D000328:Adult; D002154:Calpain / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D011085:Polycystic Ovary Syndrome / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics*
D002154:Calpain; C415197:calpain 10