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Genetic Polymorphism PC-1 K121Q and Ethnic Susceptibility to Insulin Resistance

Center for Human Nutrition and the Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390

Address all correspondence and requests for reprints to: Nicola Abate, M.D., University of Texas Southwestern Medical Center, 6011 Harry Hines Boulevard, Dallas, Texas 75390-9169. E-mail: nicola.abate{at}utsouthwestern.edu.

Genetic susceptibility may be responsible for high prevalence of insulin resistance in Asian Indians. This study was carried out in samples of local Asian Indians and Caucasians to determine whether plasma cell membrane glycoprotein (PC)-1 K121Q and insulin receptor substrate-1 (IRS-1) G972A polymorphisms contribute significantly to susceptibility to insulin resistance in Asian Indians. The frequency of carrying at least one copy of the PC-1 121Q variant in Asian Indians was significantly higher than that in Caucasians (P = 0.01), but the frequency was similar for IRS-1 972A (6% and 7%). A significantly higher insulin area under the curve during oral glucose tolerance testing (P < 0.0001) and lower insulin sensitivity during hyperinsulinemic-euglycemic clamps (P = 0.04) were found in Asian Indians with PC-1 121Q variant compared with Asian Indians with wild-type PC-1 and with Caucasians with or without the polymorphism. IRS-1 972A was not associated with any change in insulin sensitivity. We conclude that the PC-1 K121Q polymorphism associates with primary insulin resistance in migrant Asian Indians. A relatively high frequency of this polymorphism thus may be one factor contributing to insulin resistance susceptibility in Asian Indians. This finding indicates the need for expanded studies on the association between PC-1 K121Q and insulin resistance in a representative sample of the Asian Indian population.

This work was supported by NIH Grants K23-RR-16075, HL-29252, DK-42582, DK-02700, and MO1-RR-00633 (NIH/DHS/DHHS).

Abbreviations: AUC, Area under the curve; CHD, coronary heart disease; GCRC, General Clinical Research Center; HDL, high density lipoprotein; IRS, insulin receptor substrate; LDL, low density lipoprotein; OGTT, oral glucose tolerance test; PC-1, plasma cell membrane glycoprotein; Rd, rate of glucose disposal; VLDL, very low density lipoprotein.

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