[The impact of calpain-10 gene combined-SNP variation on type 2 diabetes mellitus and its related metabolic traits].
OBJECTIVE
To investigate the impact of calpain-10 gene (CAPN-10) combined single nucleotide polymorphism (SNP) variation on type 2 diabetes mellitus (T2DM) and its related clinical metabolic traits in Chinese.


METHODS
The study population consisted of 268 Chinese residents in Shanghai. Among them, 144 were subjects with normal glucose tolerance (NGT) and 124, with T2DM. Plasma glucose (PG), insulin (INS), c-peptide (CP) and free fatty acids (FFA) levels were measured at fasting and 30, 60, 120, and 180 minutes after oral 75 g glucose challenge. The islet beta-cell insulin secretion and tissue insulin sensitivity were assessed. CAPN-10 UCSNP44,-43,-19 and -63 were genotyped.


RESULTS
(1) In Chinese NGT subjects, the major allele of UCSNP-44 was allele T (frequency=91%), of UCSNP43 was G(89%), of UCSNP-19 was I (3 repeats of a 32 bp sequence) (67%) and of UCSNP-63 was C allele (79%). Significant differences were observed in comparison of these allele frequencies in Chinese to those in other ethnic groups reported in the literature. (2) 14 genotype combinations of these four SNPs were observed in Chinese NGT subjects. 69% of the NGT population was composed of four genotype combinations, in the order of UCSNP44,-43,-19 and -63, i.e., combination A:TT-GG-DI-CC(haplotype combination was 1121/1111) (frequency=10%), combination B:TT-GA-II-CC(1121/1221)(10%), combination C:TT-GG-II-CC(1121/1121)(26%) and combination D:TT-GG-DI-CT(1121/1112)(22%).(3) The frequencies of the above mentioned SNP in single or in combinations were not different significantly between NGT and T2DM groups. (4) The variation of clinical metabolic parameter levels shifted from completely normal towards abnormal glucose intolerance among genotype combination subgroups. In comparison between combination A and combination D, subjects in the former subgroups had: higher PG levels with delayed peak after glucose challenge; less and lower decrement of FFA levels after challenge with no rising in late stage; higher insulin levels with delayed peak after challenge; and the tendency of decreased insulin sensitivity. More than half of the comparisons remained statistically significant after adjusted with age, gender, body mass index and waist circumference.


CONCLUSIONS
The variation of calpain-10 gene has impact on the variation of clinical metabolic parameter levels related to type 2 diabetes mellitus. Such impact depends upon the haplotypes as well as the haplotype combination of calpain-10 gene variations.
Xiang
K
K
Shanghai Diabetes Institute, Department of Endocrinology & Metabolism, Shanghai No. 6 People Hospital, Shanghai, 200233 P.R.China. sphxiang@public.sta.net.cn
Fang
Q
Q
Zheng
T
T
Jia
W
W
Wang
Y
Y
Zhang
R
R
Li
J
J
Shen
K
K
D000483:Alleles; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D002154:Calpain / Q000235:genetics*; D004247:DNA / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics* / Q000473:pathology; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
D001786:Blood Glucose; D002096:C-Peptide; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D004247:DNA; D002154:Calpain; C415197:calpain 10