Essential hypertension (EH) is a highly heterogeneous disorder that influenced by genetic and environmental factors and their interactions (
Insulin must be mediated by insulin receptor (INSR) to perform its function.
In addition, insulin receptor substrate 1 (IRS-1) is a signaling protein widely distributed in the cytoplasm of insulin-sensitive tissues and serves a key role in signal transduction (
Considering the limited sample sizes and inconclusive results in individual studies, it is necessary to evaluate more precise results on the genetic association between the
The present meta-analysis followed the Cochrane Collaboration definition and PRISMA 2009 guidelines for meta-analysis and systematic review. A systematically search was carried out in the databases including PubMed, EMBASE, Web of Science and China National Knowledge Infrastructure. All the related publications up to January 20th, 2023 were screened by using the following search strategy: ‘insulin receptor’ or ‘
Inclusion criteria: i) Papers were case-control designed; ii) studies referred to the genetic association between
Exclusion criteria: i) Papers were duplicates; ii) papers were abstracts, letters, short communication, review or case report; iii) studies had unavailable data in case or control group.
The following information was extracted: First author's name, year of publication, ethnicity, mean ages, sex ratio (male%), body mass index, systolic pressure, diastolic blood pressure, methods of genotyping, number of cases and controls, number of genotypes in cases and controls. Authors Yan Wang and Qin Xiang conducted the data extraction independently. When there were discrepancies between the two authors, discussion was applied to resolve the inconsistencies. The quality assessment was performed by using Newcastle-Ottawa Scale (NOS). Studies with a score of ≥6 was included in the present meta-analysis study.
Combined ORs and 95% CIs were used to evaluate the relationship of the
A total of 433 studies were originally obtained. Among which, 121 studies were excluded for being duplicates, 185 studies were excluded for being unrelated to the association of
The combined ORs for the allele [P=0.94, OR=1.02, (95% CI)=(0.68, 1.53)], dominant [P=0.91, OR=0.98, (95% CI)=(0.65, 1.46)] and recessive models [P=0.68, OR=1.25, (95% CI)=(0.44, 3.52)] of
In addition, significant associations were found for the allele [P=0.0008, OR=0.58, (95% CI)=(0.42, 0.80)], dominant [P=0.02, OR=0.59, (95% CI)=(0.38, 0.92)] and recessive models [P=0.003, OR=0.38, (95% CI)=(0.20, 0.72)] of
Furthermore, the pooled ORs for all the genetic models of
Significant heterogeneities were found in the allele, dominant, and recessive models of
Publication bias in the included studies was assessed using the Begg's funnel plot and Egger's linear regression test. The shapes of the Begg's funnel plot did not reveal any evidence of obvious asymmetry for
INSR gene mutation can affect receptor function in several ways: i) Reduced receptor synthesis rate; ii) abnormal receptor embedding process; iii) decreased affinity between the receptor and insulin; iv) decreased tyrosine kinase activity; and v) accelerated receptor degradation (
The nucleotide at INSR exon 8 6244 loci is mutated from G to A, resulting in NsiI polymorphism (
The
Limitations of this study should also be considered. First, the number of included studies and subjects in the present study were relatively small, which might partly reduce the calculation power for the association between the
The data of the present study suggested that the
Not applicable.
All data generated or analyzed during this study are included in this published article.
LT and JML participated in study design and data collection, carried out the initial analysis and drafted the article. YW and QX aided in data acquisition, data analysis and statistical analysis. LT and YW carried out literature search, data acquisition and manuscript editing. QX and JML confirm the authenticity of all the raw data. TL and JML performed manuscript review. All authors have read and approved the final manuscript.
Not applicable.
Not applicable.
The authors declare that they have no competing interests.
Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow chart of studies inclusion and exclusion.
Forest plots of odds ratios for the association between INSR NsiI and hypertension. (A) Allelic model; (B) dominant model and (C) recessive model.
Forest plots of odds ratios for the association between INSR RsaI and hypertension. (A) Allelic model; (B) dominant model and (C) recessive model.
Forest plots of odds ratios for the association between ISR-1 G972R and hypertension. (A) Allelic model; (B) dominant model and (C) recessive model.
Sensitivity analyses between INSR NsiI, RsaI and ISR-1 G972R and hypertension. (A) INSR NsiI; (B) INSR RsaI; (C) ISR-1 G972R.
Publication bias of literatures for allelic model of INSR NsiI was tested by Begg's funnel plot and Egger's test. The Begg's funnel plot and Egger's test of INSR RsaI and ISR-1 G972R were not performed for lack of data.
Characters of eligible studies in the present study.
First author, year | Ethnicity | Age | Sex (M%) (case/control) | BMI (case/control) | SBP (case/control) | DBP (case/control) | Genotyping methods | Case | Control | NOS | (Refs.) |
---|---|---|---|---|---|---|---|---|---|---|---|
Ao, 2006 | Chinese | 52.40±12.34/ 43.54±9.79 | 38.1/39.7 | 26.65±4.37/ 25.40±3.61 | NA | NA | PCR-RFLP | 84 | 199 | 6 | ( |
Kang, 2000 | Korean | NA/NA | NA | NA | NA | NA | PCR-RFLP | 86 | 134 | 6 | ( |
Lin, 2000 | Chinese | 53. 36±10.12/ 49. 47±9.59 | 55.0/62.8 | 24.91±3.22/ 25.08±2.74 | 169.15±28.36/ 170.48±10.36 | 7.98±16.15/ 8.76±8.44 | PCR-RFLP | 120 | 86 | 8 | ( |
Schrader, 1996 | Australian | 52±12/46±10 | 46.3/62.7 | 26.2±4.5/ 25.4±4.3 | 176±24/ 116±9 | 111±18/ 73±8 | PCR-RFLP | 134 | 126 | 8 | ( |
Yu, 2007 | Chinese | 53.36±10.12/ 49.47±9.59 | 36.7/44.6 | 23.00±3.54/ 24.88±4.25 | 177.01±17.25/ 114.00±11.53 | 98.31±13.54/ 75.23±9.14 | PCR-RFLP | 221 | 204 | 8 | ( |
Zhu, 2009 | Chinese | 63.52±4.60/ 63.94±4.84 | 55.8/60.6 | 25.37±2.69/ 24.34±2.60 | 162±12/ 123±11 | 95±9/77±7 | PCR-RFLP | 190 | 94 | 8 | ( |
Morris, 1993 | Australia | 50±14/46±19 | 54.0/61.0 | 25±5/NA | 176±22/ 113±7 | 114±22/ 71±5 | PCR-RFLP | 85 | 100 | 8 | ( |
Ying, 1991 | Australia | 51±14/40±11 | NA | NA | NA | NA | PCR-RFLP | 67 | 75 | 6 | ( |
Wang, 2007 | Chinese | 51.22±10.86/ 53±11.85 | 55.8/58.0 | 26.48±4.09/ 24. 25±3.56 | NA | NA | PCR-RFLP | 120 | 100 | 7 | ( |
Xu, 2006 | Chinese | 52.71±12.16/ 44.03±10.55 | 37.6/47.3 | 26.88±4.31/ 25.55±3.97 | NA | NA | PCR-RFLP | 182 | 375 | 7 | ( |
M, male; BMI, Body Mass Index; SBP, Systolic pressure; DBP, Diastolic blood pressure; NOS, Newcastle-Ottawa Scale; NA, Not available.
Genetic association between the
Test of association | Test of heterogeneity | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Gene/polymorphism | Minor allele frequency | Genetic models | Ethnicity | Number of studies | OR | 95% CI | P-value | Model | P-value | I2 (%) |
INSR/Nsil | Unavailable | Allele | Total | 6 | 1.02 | (0.68, 1.53) | 0.94 | R | 0.003 | 73 |
Asian | 5 | 1.11 | (0.69, 1.78) | 0.66 | R | 0.007 | 71 | |||
Caucasian | 1 | 0.72 | (0.48, 1.07) | 0.11 | - | - | - | |||
Dominant | Total | 6 | 0.98 | (0.65, 1.46) | 0.91 | R | 0.02 | 63 | ||
Asian | 5 | 1.06 | (0.67, 1.69) | 0.80 | R | 0.03 | 63 | |||
Caucasian | 1 | 0.70 | (0.43, 1.14) | 0.15 | - | - | - | |||
Recessive | Total | 6 | 1.25 | (0.44, 3.52) | 0.68 | R | 0.08 | 53 | ||
Asian | 5 | 1.97 | (0.75, 5.22) | 0.17 | R | 0.25 | 27 | |||
Caucasian | 1 | 0.45 | (0.13, 1.55) | 0.21 | - | - | - | |||
INSR/Rsal | Unavailable | Allele | Total | 2 | 0.58 | (0.42, 0.80) | 0.0008 | R | 0.96 | 0 |
Asian | 0 | - | - | - | - | - | - | |||
Caucasian | 2 | 0.58 | (0.42, 0.80) | 0.0008 | R | 0.96 | 0 | |||
Dominant | Total | 2 | 0.59 | (0.38, 0.92) | 0.02 | R | 0.87 | 0 | ||
Asian | 0 | - | - | - | - | - | - | |||
Caucasian | 2 | 0.59 | (0.38, 0.92) | 0.02 | R | 0.87 | 0 | |||
Recessive | Total | 2 | 0.38 | (0.20, 0.72) | 0.003 | R | 0.93 | 0 | ||
Asian | 0 | - | - | - | - | - | - | |||
Caucasian | 2 | 0.38 | (0.20, 0.72) | 0.003 | R | 0.93 | 0 | |||
ISR-1/G972R | T=0.062104/ | Allele | Total | 2 | 1.66 | (0.52, 5.28) | 0.39 | F | 0.99 | 0 |
11306 (ALFA) | Asian | 2 | 1.66 | (0.52, 5.28) | 0.39 | F | 0.99 | 0 | ||
Caucasian | 0 | - | - | - | - | - | - | |||
Dominant | total | 2 | 1.67 | (0.52, 5.33) | 0.39 | F | 0.99 | 0 | ||
Asian | 2 | 1.67 | (0.52, 5.33) | 0.39 | F | 0.99 | 0 | |||
Caucasian | 0 | - | - | - | - | - | - | |||
Recessive | Total | 2 | 1.66 | (0.52, 5.28) | 0.39 | F | 0.99 | 0 | ||
Asian | 2 | 1.66 | (0.52, 5.28) | 0.39 | F | 0.99 | 0 | |||
Caucasian | 0 | - | - | - | - | - | - |
ALFA, Allele Frequency Aggregator; INSR, insulin receptor; IRS-1, insulin receptor substrate-1; OR, odds ratios; CI, confidence interval; F, fixed model; R, Random model.