Association of Insulin Gene VNTR Polymorphism with Polycystic Ovary Syndrome

Abstract

Variability in the number of tandem repeats of the insulin gene (INS VNTR) is known to influence several phenotypes, including polycystic ovary syndrome (PCOS), diabetes mellitus type 1, diabetes mellitus type 2, and birth weight. The presence of the class III allele of INS VNTR has been reported to be protective in diabetes mellitus type 1, but in contrary it increases the disease risk of PCOS and diabetes mellitus type 2. PCOS is a very common endocrinopathy in women of reproductive age. The etiology of PCOS is uncertain, but family history of this syndrome suggests a major genetic cause. The aim of this pilot study was to investigate the possible association of INS VNTR polymorphism with PCOS in Czech women. In PCOS, significantly higher WHR, BMI, G0, G180, I30, Cp0, Cp30, Cp60, AUC‐I, AUC‐Cp, and insulinogenic index and significantly lower AUC‐G/AUC‐I were found. No significant differences in INS VNTR genotype, phenotype, or allele frequencies were found between PCOS and controls. In spite of several differences in anthropometric and biochemical parameters (abdominal fat localization, increased β‐cell function, and lower insulin sensitivity in PCOS women), no effect of INS VNTR polymorphism was found on insulin secretion, insulin action, or any other screened parameter.

Low-density lipoprotein receptor–related protein-5 C/T polymorphism in exon 18 is associated with C peptide and proinsulin levels in control women and patients with polycystic ovary syndrome

“…Moreover, paternal transmission of class III alleles from heterozygous fathers to anovulatory patients with PCOS was more frequent than was maternal transmission (38,39). However, later case-control studies did not confirm these associations (7,40,41).…”

“…The issue of b-cell function in PCOS remains even more controversial, with findings ranging from increased to defective insulin secretion (2)(3)(4)(5)(6)(7)(8). Genetic factors determine not only insulin resistance but also, and probably more strongly, insulin secretion (9).…”

Association of insulin gene variable number of tandem repeats regulatory polymorphism with polycystic ovary syndrome

“…Our initial search identified a total of 476 potentially eligible articles. Based on our inclusion criteria, a total of 8 articles were involved in this meta-analysis [10,[12][13][14][15][16][17][18]. There was perfect inter-rater reliability for the selection of studies to be included in the meta-analysis, with Kappa values of 0.834 based on titles and abstracts and 0.857 based on full texts.…”

“…Another family-based study also showed that PCOS was associated with the III alleles [11]. In addition, numerous genetic associated studies with case-control design have focused on the association of INS VNTR and POCS [10,[12][13][14][15][16][17][18]. However, results of different studies have been inconsistent, suggesting that it is unclear whether INS VNTR is associated with PCOS or not.…”

Lack of association of INS VNTR polymorphism with polycystic ovary syndrome: a meta-analysis

“…In total, 13 case-control studies [21][22][23][24][25][26][27][28][29][30] including 1,767 cases and 4,181 controls, were included in the analysis. Waterworth DM [21] and Powell BL [23] were conducted on the anovulatory PCOS.…”