Linkage and association of insulin gene VNTR regulatory polymorphism with polycystic ovary syndrome.

Waterworth, D; Bennett, S; Gharani, N; McCarthy, M; Hague, S; Batty, S; Conway, G; White, D; Todd, J; Franks, S; Williamson, R

Women's Health Collection

Journal article

Linkage and association of insulin gene VNTR regulatory polymorphism with polycystic ovary syndrome.

Abstract:: BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting up to 10% of women of reproductive age. Women with anovulatory PCOS have hyperinsulinaemia, insulin resistance, and dyslipidaemia, and the syndrome is associated with greatly increased risks of non-insulin-dependent diabetes mellitus and cardiovascular disease and it often clusters in families. The VNTR (variable number of tandem repeats) locus upstream of the insulin gene (INS) regulates insulin expression. We have studied INS VNTR as a candidate genetic locus for susceptibility to PCOS. METHODS: We evaluated linkage of PCOS to the INS VNTR locus on chromosome 11p15.5 in 17 families with several cases, and looked for an association between VNTR and PCOS in two additional clinic populations. VNTR genotypes were designated I/I, I/III, and III/III and linkage disequilibrium mapping was used to test the primary role of the VNTR. FINDINGS: In a group of PCOS/male pattern baldness families, we obtained positive evidence for linkage to 11p15.5 (p = 0.002). The INS VNTR III/III genotype was associated with an increased risk of PCOS in two independent case-control studies (odds ratios 8.20 [p = 0.005] and 5.70 [p = 0.043]). Multilocus linkage disequilibrium mapping suggests that VNTR itself is the predisposing locus. INTERPRETATION: Mapping of susceptibility to PCOS to the INS VNTR implies that PCOS is due, in part, to an inherited alteration in insulin production. The data suggest a mechanistic link between type 2 diabetes and PCOS, which is a risk factor for diabetes later in life.

Publication status:: Published

Actions

Email

Email this record

Send the bibliographic details of this record to your email address.

Your Email
Please enter the email address that the record information will be sent to.

-
Your message (optional)
Please add any additional information to be included within the email.
Share
Cite

Cite this record

APA Style

Waterworth, D., Bennett, S., Gharani, N., McCarthy, M., Hague, S., Batty, S., Conway, G., White, D., Todd, J., Franks, S., & Williamson, R. (1997). Linkage and association of insulin gene VNTR regulatory polymorphism with polycystic ovary syndrome. Lancet, 349(9057), 986–990.

MLA Style

Waterworth, D, et al. “Linkage and Association of Insulin Gene VNTR Regulatory Polymorphism with Polycystic Ovary Syndrome.” Lancet, vol. 349, no. 9057, 1997, pp. 986–90.

Chicago Style

Waterworth, D, S Bennett, N Gharani, et al. 1997. “Linkage and Association of Insulin Gene VNTR Regulatory Polymorphism with Polycystic Ovary Syndrome.” Lancet 349 (9057): 986–90.
Print