Distribution of neuropeptide Y Leu7Pro polymorphism in patients with type 1 diabetes and diabetic nephropathy among Swedish and American populations.
OBJECTIVE
The distribution of Leu7Pro polymorphism in the neuropeptide Y gene shows a geographical north to south gradient of decreasing frequency, suggesting that it may be a population-specific causal variant. This polymorphism is found to be associated with diabetic nephropathy (DN) and coronary heart disease in Finnish women with type 1 diabetes (T1D). The present study aims to evaluate the susceptibility of this polymorphism to the development of DN in two different populations.


METHODS
One sample set consists of 174 (females 98 and males 76) Swedish T1D patients with DN and 249 (females 132 and males 117) patients without DN. Another sample set includes 597 (females 356 and males 241) American T1D patients without DN and 577 (females 264 and males 313) patients with DN, who were descents of European Caucasians and were from the Genetics of Kidneys in Diabetes (GoKinD) Study.


METHODS
Genotyping of Leu7Pro polymorphism was performed by dynamic allele-specific hybridization.


RESULTS
The C allele frequencies of Leu7Pro polymorphism in T1D patients between Swedish and American GoKinD populations were significantly different (6.3 vs 4.0%; P=0.006). Particularly, the C allele frequency in Swedish female T1D patients with DN was significantly higher in comparison with T1D patients without DN (10.2 vs 4.2%; P=0.011, OR=2.614, 95% confidence intervals: 1.249-5.467). No significant association of this polymorphism with DN was observed in Swedish male T1D patients and the patients from GoKinD.


CONCLUSIONS
The present study provides further evidence that Leu7Pro polymorphism confers the susceptibility to the development of DN in Swedish female T1D patients.
Ma
Jun
J
Department of Molecular Medicine and Surgery, L6:B2, Karolinska Institutet, Rolf Luft Center for Diabetes Research, Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
Nordman
Sofia
S
Möllsten
Anna
A
Falhammar
Henrik
H
Brismar
Kerstin
K
Dahlquist
Gisela
G
Efendic
Suad
S
Gu
Harvest F
HF
D000328:Adult; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D007930:Leucine / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009478:Neuropeptide Y / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011392:Proline / Q000235:genetics*; D013548:Sweden / Q000453:epidemiology; D014481:United States / Q000453:epidemiology
D009478:Neuropeptide Y; D011392:Proline; D007930:Leucine