Ppp1r3

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Plasma cell membrane glycoprotein-1 (PC-1)

A promoter VNTR was linked and associated with PCOS and/or insulin sensitivity in women with polycystic ovaries in some studies but not others. Analysis of multiple data sets showed no association of the VNTR with PCOS or testosterone levels.

An SNP in the tyrosine kinase domain was associated with PCOS, particularly in lean women. Other studies of the insulin receptor in women with PCOS have identified only common, silent polymorphisms.

Two independent studies have reported linkage and association of the micro satellite marker D19S884 with PCOS. A study of

Italian and Spanish women with PCOS failed to confirm this association.

Variants of both IRS1 and IRS2 were found to influence fasting insulin and postload glucose levels, respectively, in women with PCOS. IRS1 was associated with PCOS and with adolescent hyperandrogenism and obese insulin-resistant PCOS.

IRS1 genotype influenced response to metformin in PCOS. IRS1 was not found to be linked or associated with PCOS or hyperandrogenemia in other studies.

One study found the 112/121 haplotype combination associated with a 2-fold increased risk of PCOS, but a larger study showed no such association. Two different studies from Spain produced conflicting results regarding association of SNP-44 with PCOS.

In Caucasian but not African American women with PCOS, the Prol2Ala variant was found to be associated with less insulin resistance. A marker near PPARG was not linked or associated with PCOS. Prol2Ala influenced body mass index in hyperandrogenic adolescents. Prol2Ala was associated with insulin sensitivity and lower hirsutism in German PCOS patients. Prol2Ala associated with obesity and increased insulin sensitivity in Turkish PCOS cases and controls. Prol2Ala associated with PCOS in a Finnish study. Negative association studies of Prol2Ala were also reported.

A promoter variant was not associated with PCOS; however, it was associated with body mass index in PCOS.

An SNP in IGF2 was associated with PCOS in a small study.

A single variant was associated with insulin response to glucose challenge and hyperandrogenemia in PCOS.

A coding SNP was associated with PCOS.

Negative studies have also been published concerning IGF-1, IGF-1 receptor. IGFBP1, IGFBP3. Leydig insulin-like protein 3. SORBS1, IGF-2 receptor, and PTP1B. Negative linkage and association studies of genes relating to obesity and fuel metabolism in PCOS have been published concerning leptin and leptin receptor, glucocorticoid receptor, glycogen synthase, melanocortin 4 receptor, proopiomelanocortin, and uncoupling proteins 2 and 3. PCOS. polycystic ovary syndrome; VNTR, variable number tandem repeat; SNP, single nucleotide polymorphism.

Table 4

Published Candidate Gene Studies in PCOS: Cardiovascular Disease

Table 4

Published Candidate Gene Studies in PCOS: Cardiovascular Disease

Genes

Comments

Paraoxonase

An SNP in paraoxonase was associated with PCOS in a small study.

PAI-1 (plasminogen

A promoter variant was associated with PCOS and increased PAI-1 levels.

activator inhibitor-1)

Negative association of PAI-1 with PCOS was also reported.

IL-6 (interleukin-6)

Two promoter SNPs were associated with PCOS. In another study, one of

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